Sequential morphometric evaluation at UnicCa® and DCD® implant surfaces. An experimental study in the dog

Abstract

Aim

To study tissue components adjacent to implants with nanotechnologically modified surfaces at different periods of healing.

Material & methods

In 12 beagle dogs, two different implant systems with different surface configurations were randomly installed in the edentulous premolar regions of the mandible.

One surface was first acid-etched and subsequently, nanotechnologically modified with calcium ions (UnicCa^®), while the other was first sandblasted and acid-etched, and then additionally treated with a nanometer calcium phosphate deposition (discrete crystalline deposition; DCD^®). The implants were fully submerged; surgeries and sacrifices were planned to harvest biopsies after 1, 2, 4 and 8 weeks of healing (n = 6 per period).

A morphometric evaluation of percentages of new and old bone, bone debris/particles and clot, new soft tissues (provisional matrix and immature marrow), mature bone marrow and vessels was performed in the spongiosa compartment adjacent to the implant surface up to a distance of about 0.4 mm from the surface.

Results

After 2 weeks of healing, the soft tissues were represented by 41.0% at the UnicCa^® and 37.9% at the DCD^® surfaces, in both cases mainly being composed of provisional matrix. These percentages decreased over time, being composed of greater amounts of immature bone marrow, and disappeared after 8 weeks. New bone increased progressively between 1 and 8 weeks of healing from 9.7 ± 6.3% to 70.0 ± 8.4% and from 8.2 ± 3.5% to 67.0 ± 6.1% at the UnicCa^® and DCD^® surfaces, respectively. Pristine bone was progressively resorbed.

Conclusions

Throughout the periods of healing observed, the formation of a provisional matrix followed by the formation of new bone and marrow was revealed in a similar fashion as for other modified surface configurations.

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Adverse reaction after hyaluronan injection for minimally invasive papilla volume augmentation. A report on two cases

Abstract

Objectives

To report two cases of adverse reaction after mucosal hyaluronan (HY) injection around implant-supported crowns, with the aim to augment the missing interdental papilla.

Material and Methods

Two patients with single, non-neighbouring, implants in the anterior maxilla, who were treated within the frames of a randomized controlled clinical trial testing the effectiveness of HY gel injection to reconstruct missing papilla volume at single implants, presented an adverse reaction. Injection of HY was performed bilaterally using a 3-step technique: (i) creation of a reservoir in the mucosa directly above the mucogingival junction, (ii) injection into the attached gingiva/mucosa below the missing papilla, and (iii) injection 2–3 mm apically to the papilla tip. The whole-injection session was repeated once after approximately 4 weeks.

Results

Both patients presented with swelling and extreme tenderness with a burning sensation on the lip next to the injection area, after the second injection session. In one of the cases, a net-like skin discoloration (livedo reticularis) was also noted. The symptoms lasted for up to 7 days, and in both cases, symptoms resolved without any signs of skin or mucosal necrosis or any permanent damage.

Conclusion

Most likely, water attraction over time by the highly hygroscopic HY, exerted progressively an external vascular compression and at least partial occlusion of neighbouring blood vessels. An infection or an allergic reaction seems unlikely, since all symptoms gradually disappeared within a week irrespective use of antimicrobials, while an allergic reaction most likely would not have been restricted to one side.

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Primary Cilia and Intraflagellar Transport Proteins in Bone and Cartilage

Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of human pleiotropic syndromes called Ciliopathies. Some of the ciliopathies display skeletal dysplasias, implying the important role of primary cilia in skeletal development and homeostasis. Emerging evidence has shown that loss or malfunction of primary cilia or ciliary proteins in bone and cartilage is associated with developmental and function defects. Intraflagellar transport (IFT) proteins are essential for cilia formation and/or function. In this review, we discuss the role of primary cilia and IFT proteins in the development of bone and cartilage, as well as the differentiation and mechanotransduction of mesenchymal stem cells, osteoblasts, osteocytes, and chondrocytes. We also include the role of primary cilia in tooth development and highlight the current advance of primary cilia and IFT proteins in the pathogenesis of cartilage diseases, including osteoarthritis, osteosarcoma, and chondrosarcoma.

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Developmental Regulation of the Growth Plate and Cranial Synchondrosis

Long bones and the cranial base are both formed through endochondral ossification. Elongation of long bones is primarily through the growth plate, which is a cartilaginous structure at the end of long bones made up of chondrocytes. Growth plate chondrocytes are organized in columns along the longitudinal axis of bone growth. The cranial base is the growth center of the neurocranium. Synchondroses, consisting of mirror-image growth plates, are critical for cranial base elongation and development. Over the last decade, considerable progress has been made in determining the roles of the parathyroid hormone–related protein, Indian hedgehog, fibroblast growth factor, bone morphogenetic protein, and Wnt signaling pathways in various aspects of skeletal development. Furthermore, recent evidence indicates the important role of the primary cilia signaling pathway in bone elongation. Here, we review the development of the growth plate and cranial synchondrosis and the regulation by the above-mentioned signaling pathways, highlighting the similarities and differences between these 2 structures.

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Sequential morphometric evaluation at UnicCa® and DCD® implant surfaces. An experimental study in the dog

Abstract

Aim

To study tissue components adjacent to implants with nanotechnologically modified surfaces at different periods of healing.

Material & methods

In 12 beagle dogs, two different implant systems with different surface configurations were randomly installed in the edentulous premolar regions of the mandible.

One surface was first acid-etched and subsequently, nanotechnologically modified with calcium ions (UnicCa^®), while the other was first sandblasted and acid-etched, and then additionally treated with a nanometer calcium phosphate deposition (discrete crystalline deposition; DCD^®). The implants were fully submerged; surgeries and sacrifices were planned to harvest biopsies after 1, 2, 4 and 8 weeks of healing (n = 6 per period).

A morphometric evaluation of percentages of new and old bone, bone debris/particles and clot, new soft tissues (provisional matrix and immature marrow), mature bone marrow and vessels was performed in the spongiosa compartment adjacent to the implant surface up to a distance of about 0.4 mm from the surface.

Results

After 2 weeks of healing, the soft tissues were represented by 41.0% at the UnicCa^® and 37.9% at the DCD^® surfaces, in both cases mainly being composed of provisional matrix. These percentages decreased over time, being composed of greater amounts of immature bone marrow, and disappeared after 8 weeks. New bone increased progressively between 1 and 8 weeks of healing from 9.7 ± 6.3% to 70.0 ± 8.4% and from 8.2 ± 3.5% to 67.0 ± 6.1% at the UnicCa^® and DCD^® surfaces, respectively. Pristine bone was progressively resorbed.

Conclusions

Throughout the periods of healing observed, the formation of a provisional matrix followed by the formation of new bone and marrow was revealed in a similar fashion as for other modified surface configurations.

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Adverse reaction after hyaluronan injection for minimally invasive papilla volume augmentation. A report on two cases

Abstract

Objectives

To report two cases of adverse reaction after mucosal hyaluronan (HY) injection around implant-supported crowns, with the aim to augment the missing interdental papilla.

Material and Methods

Two patients with single, non-neighbouring, implants in the anterior maxilla, who were treated within the frames of a randomized controlled clinical trial testing the effectiveness of HY gel injection to reconstruct missing papilla volume at single implants, presented an adverse reaction. Injection of HY was performed bilaterally using a 3-step technique: (i) creation of a reservoir in the mucosa directly above the mucogingival junction, (ii) injection into the attached gingiva/mucosa below the missing papilla, and (iii) injection 2–3 mm apically to the papilla tip. The whole-injection session was repeated once after approximately 4 weeks.

Results

Both patients presented with swelling and extreme tenderness with a burning sensation on the lip next to the injection area, after the second injection session. In one of the cases, a net-like skin discoloration (livedo reticularis) was also noted. The symptoms lasted for up to 7 days, and in both cases, symptoms resolved without any signs of skin or mucosal necrosis or any permanent damage.

Conclusion

Most likely, water attraction over time by the highly hygroscopic HY, exerted progressively an external vascular compression and at least partial occlusion of neighbouring blood vessels. An infection or an allergic reaction seems unlikely, since all symptoms gradually disappeared within a week irrespective use of antimicrobials, while an allergic reaction most likely would not have been restricted to one side.

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Prediction of individual implant bone levels and the existence of implant “phenotypes”

Abstract

Objectives

To cluster implants placed in patients of a private practice and identify possible implant "phenotypes" and predictors of individual implant mean bone levels (IIMBL).

Materials and methods

Clinical and radiographical variables were collected from 72 implant-treated patients with 237 implants and a mean 7.4 ± 3.5 years of function. We clustered implants using the k-means method guided by multidimensional unfolding. For predicting IIMBL, we used principal component analysis (PCA) as a variable reduction method for an ensemble selection (ES) and a support vector machines models (SVMs). Network analysis investigated variable interactions.

Results

We identified a cluster of implants susceptible to peri-implantitis (96% of the implants in the cluster were affected by peri-implantitis) and two overlapping clusters of implants resistant to peri-implantitis. The cluster susceptible to peri-implantitis showed a mean IIMBL of 5.2 mm and included implants placed mainly in the lower front jaw and in mouths having a mean of eight teeth. PCA extracted the parameters such as number of teeth, full-mouth plaque scores, implant surface, periodontitis severity, age and diabetes as significant in explaining the data variability. ES and SVMs showed good results in predicting IIMBL (root-mean-squared error of 0.133 and 0.149, 10-fold cross-validation error of 0.147 and 0.150, respectively). Network analysis revealed limited interdependencies of variables among peri-implantitis-affected and non-affected implants and supported the hypothesis of the existence of distinct implant "phenotypes."

Conclusion

Two implant "phenotypes" were identified, one with susceptibility and another with resistance to peri-implantitis. Prediction of IIMBL could be achieved by using six variables.

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Coronary spasm secondary to biphasic anaphylaxis after hymenoptera stings

Publication date: Available online 1 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Miguel Ángel Blasco-Navalpotro, Alberto Orejas-Gallego, José Luis Flordelís-Lasierra, Nieves Prior-Gómez, Juana Jiménez-Jiménez, Francisco Javier Seoane-Leston




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Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber

Publication date: Available online 1 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Yusuke Okuma, Yoshitaka Okamoto, Syuji Yonekura, Tomohisa Iinuma, Toshioki Sakurai, Sawako Hamasaki, Yuji Ohki, Heizaburo Yamamoto, Daiju Sakurai
BackgroundImmediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis.ObjectiveTo examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC).MethodsFifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m³ for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored.ResultsThe severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased.ConclusionVarious mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure.



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Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer

Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer:

Abstract

Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival. Since 2013 nab-paclitaxel (paclitaxel-albumin-bound particles) became a new treatment option for patients with metastatic pancreatic cancer based on the results of MPACT trial. Moreover, encouraging activity in PDAC of the combination regimen of paclitaxel and carboplatin that is being widely used in other solid tumors has been reported recently. Biomarkers, including biomarkers predictive of taxane resistance, could allow individualized tailored therapy. BRCA mutation status could serve as predictor of better chemotherapy treatment outcome in PDAC. The present review summarizes the principal clinical trials evaluating the efficacy of taxanes both as monotherapy and in combination in view of the potential use in the treatment of PDAC.

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Letter: a simple out-patient faecal microbiota transplant technique

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Letter: oral low-dose methotrexate for collagenous colitis

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Letter: anti-TNF in steroid-dependent ulcerative colitis - are the available data enough?

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Letter: oral low-dose methotrexate for collagenous colitis – authors’ reply

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis – authors’ reply

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis

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Editors’ Declarations of Interest

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Primary Cilia and Intraflagellar Transport Proteins in Bone and Cartilage

Primary cilia, present on most mammalian cells, function as a sensor to sense the environment change and transduce signaling. Loss of primary cilia causes a group of human pleiotropic syndromes called Ciliopathies. Some of the ciliopathies display skeletal dysplasias, implying the important role of primary cilia in skeletal development and homeostasis. Emerging evidence has shown that loss or malfunction of primary cilia or ciliary proteins in bone and cartilage is associated with developmental and function defects. Intraflagellar transport (IFT) proteins are essential for cilia formation and/or function. In this review, we discuss the role of primary cilia and IFT proteins in the development of bone and cartilage, as well as the differentiation and mechanotransduction of mesenchymal stem cells, osteoblasts, osteocytes, and chondrocytes. We also include the role of primary cilia in tooth development and highlight the current advance of primary cilia and IFT proteins in the pathogenesis of cartilage diseases, including osteoarthritis, osteosarcoma, and chondrosarcoma.

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Developmental Regulation of the Growth Plate and Cranial Synchondrosis

Long bones and the cranial base are both formed through endochondral ossification. Elongation of long bones is primarily through the growth plate, which is a cartilaginous structure at the end of long bones made up of chondrocytes. Growth plate chondrocytes are organized in columns along the longitudinal axis of bone growth. The cranial base is the growth center of the neurocranium. Synchondroses, consisting of mirror-image growth plates, are critical for cranial base elongation and development. Over the last decade, considerable progress has been made in determining the roles of the parathyroid hormone–related protein, Indian hedgehog, fibroblast growth factor, bone morphogenetic protein, and Wnt signaling pathways in various aspects of skeletal development. Furthermore, recent evidence indicates the important role of the primary cilia signaling pathway in bone elongation. Here, we review the development of the growth plate and cranial synchondrosis and the regulation by the above-mentioned signaling pathways, highlighting the similarities and differences between these 2 structures.

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Sequential morphometric evaluation at UnicCa® and DCD® implant surfaces. An experimental study in the dog

Abstract

Aim

To study tissue components adjacent to implants with nanotechnologically modified surfaces at different periods of healing.

Material & methods

In 12 beagle dogs, two different implant systems with different surface configurations were randomly installed in the edentulous premolar regions of the mandible.

One surface was first acid-etched and subsequently, nanotechnologically modified with calcium ions (UnicCa^®), while the other was first sandblasted and acid-etched, and then additionally treated with a nanometer calcium phosphate deposition (discrete crystalline deposition; DCD^®). The implants were fully submerged; surgeries and sacrifices were planned to harvest biopsies after 1, 2, 4 and 8 weeks of healing (n = 6 per period).

A morphometric evaluation of percentages of new and old bone, bone debris/particles and clot, new soft tissues (provisional matrix and immature marrow), mature bone marrow and vessels was performed in the spongiosa compartment adjacent to the implant surface up to a distance of about 0.4 mm from the surface.

Results

After 2 weeks of healing, the soft tissues were represented by 41.0% at the UnicCa^® and 37.9% at the DCD^® surfaces, in both cases mainly being composed of provisional matrix. These percentages decreased over time, being composed of greater amounts of immature bone marrow, and disappeared after 8 weeks. New bone increased progressively between 1 and 8 weeks of healing from 9.7 ± 6.3% to 70.0 ± 8.4% and from 8.2 ± 3.5% to 67.0 ± 6.1% at the UnicCa^® and DCD^® surfaces, respectively. Pristine bone was progressively resorbed.

Conclusions

Throughout the periods of healing observed, the formation of a provisional matrix followed by the formation of new bone and marrow was revealed in a similar fashion as for other modified surface configurations.

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Adverse reaction after hyaluronan injection for minimally invasive papilla volume augmentation. A report on two cases

Abstract

Objectives

To report two cases of adverse reaction after mucosal hyaluronan (HY) injection around implant-supported crowns, with the aim to augment the missing interdental papilla.

Material and Methods

Two patients with single, non-neighbouring, implants in the anterior maxilla, who were treated within the frames of a randomized controlled clinical trial testing the effectiveness of HY gel injection to reconstruct missing papilla volume at single implants, presented an adverse reaction. Injection of HY was performed bilaterally using a 3-step technique: (i) creation of a reservoir in the mucosa directly above the mucogingival junction, (ii) injection into the attached gingiva/mucosa below the missing papilla, and (iii) injection 2–3 mm apically to the papilla tip. The whole-injection session was repeated once after approximately 4 weeks.

Results

Both patients presented with swelling and extreme tenderness with a burning sensation on the lip next to the injection area, after the second injection session. In one of the cases, a net-like skin discoloration (livedo reticularis) was also noted. The symptoms lasted for up to 7 days, and in both cases, symptoms resolved without any signs of skin or mucosal necrosis or any permanent damage.

Conclusion

Most likely, water attraction over time by the highly hygroscopic HY, exerted progressively an external vascular compression and at least partial occlusion of neighbouring blood vessels. An infection or an allergic reaction seems unlikely, since all symptoms gradually disappeared within a week irrespective use of antimicrobials, while an allergic reaction most likely would not have been restricted to one side.

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Prediction of individual implant bone levels and the existence of implant “phenotypes”

Abstract

Objectives

To cluster implants placed in patients of a private practice and identify possible implant "phenotypes" and predictors of individual implant mean bone levels (IIMBL).

Materials and methods

Clinical and radiographical variables were collected from 72 implant-treated patients with 237 implants and a mean 7.4 ± 3.5 years of function. We clustered implants using the k-means method guided by multidimensional unfolding. For predicting IIMBL, we used principal component analysis (PCA) as a variable reduction method for an ensemble selection (ES) and a support vector machines models (SVMs). Network analysis investigated variable interactions.

Results

We identified a cluster of implants susceptible to peri-implantitis (96% of the implants in the cluster were affected by peri-implantitis) and two overlapping clusters of implants resistant to peri-implantitis. The cluster susceptible to peri-implantitis showed a mean IIMBL of 5.2 mm and included implants placed mainly in the lower front jaw and in mouths having a mean of eight teeth. PCA extracted the parameters such as number of teeth, full-mouth plaque scores, implant surface, periodontitis severity, age and diabetes as significant in explaining the data variability. ES and SVMs showed good results in predicting IIMBL (root-mean-squared error of 0.133 and 0.149, 10-fold cross-validation error of 0.147 and 0.150, respectively). Network analysis revealed limited interdependencies of variables among peri-implantitis-affected and non-affected implants and supported the hypothesis of the existence of distinct implant "phenotypes."

Conclusion

Two implant "phenotypes" were identified, one with susceptibility and another with resistance to peri-implantitis. Prediction of IIMBL could be achieved by using six variables.

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Coronary spasm secondary to biphasic anaphylaxis after hymenoptera stings

Publication date: Available online 1 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Miguel Ángel Blasco-Navalpotro, Alberto Orejas-Gallego, José Luis Flordelís-Lasierra, Nieves Prior-Gómez, Juana Jiménez-Jiménez, Francisco Javier Seoane-Leston




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Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber

Publication date: Available online 1 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Yusuke Okuma, Yoshitaka Okamoto, Syuji Yonekura, Tomohisa Iinuma, Toshioki Sakurai, Sawako Hamasaki, Yuji Ohki, Heizaburo Yamamoto, Daiju Sakurai
BackgroundImmediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis.ObjectiveTo examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC).MethodsFifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m³ for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored.ResultsThe severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased.ConclusionVarious mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure.



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Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer

Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer:

Abstract

Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival. Since 2013 nab-paclitaxel (paclitaxel-albumin-bound particles) became a new treatment option for patients with metastatic pancreatic cancer based on the results of MPACT trial. Moreover, encouraging activity in PDAC of the combination regimen of paclitaxel and carboplatin that is being widely used in other solid tumors has been reported recently. Biomarkers, including biomarkers predictive of taxane resistance, could allow individualized tailored therapy. BRCA mutation status could serve as predictor of better chemotherapy treatment outcome in PDAC. The present review summarizes the principal clinical trials evaluating the efficacy of taxanes both as monotherapy and in combination in view of the potential use in the treatment of PDAC.

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Letter: a simple out-patient faecal microbiota transplant technique

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Letter: oral low-dose methotrexate for collagenous colitis

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Letter: anti-TNF in steroid-dependent ulcerative colitis - are the available data enough?

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Letter: oral low-dose methotrexate for collagenous colitis – authors’ reply

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis – authors’ reply

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis

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Editors’ Declarations of Interest

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Coronary spasm secondary to biphasic anaphylaxis after hymenoptera stings

Publication date: Available online 1 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Miguel Ángel Blasco-Navalpotro, Alberto Orejas-Gallego, José Luis Flordelís-Lasierra, Nieves Prior-Gómez, Juana Jiménez-Jiménez, Francisco Javier Seoane-Leston




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Persistent nasal symptoms and mediator release after continuous pollen exposure in an environmental challenge chamber

Publication date: Available online 1 June 2016
Source:Annals of Allergy, Asthma & Immunology
Author(s): Yusuke Okuma, Yoshitaka Okamoto, Syuji Yonekura, Tomohisa Iinuma, Toshioki Sakurai, Sawako Hamasaki, Yuji Ohki, Heizaburo Yamamoto, Daiju Sakurai
BackgroundImmediate- and late-phase reactions are associated with nasal symptoms of patients with allergic rhinitis.ObjectiveTo examine the symptoms and mediators released after continuous allergen exposure in an environmental challenge chamber (ECC).MethodsFifteen patients with Japanese cedar pollinosis were enrolled in this study and continuously exposed to cedar pollen at a concentration of 8,000 grains/m³ for 3 hours in an ECC. Nasal function tests were performed, and nasal secretions were collected before pollen exposure (0 hour), immediately after exiting the ECC (3 hours), and 6 hours after exiting the ECC (9 hours). Symptom scores were recorded every 30 minutes in the ECC and every 3 hours after exiting the ECC. The frequency of sneezing and nose blowing also was monitored.ResultsThe severity of symptoms in the ECC peaked approximately 2 hours after the beginning of pollen exposure and continued more than 6 hours after leaving the ECC. Concentrations of histamine, tryptase, interleukins 5, 3, 33, and 31, and substance P increased over time, whereas that of nasal fractional exhaled nitric oxide decreased.ConclusionVarious mediators are released during continuous allergen exposure, which subsequently induce persistent nasal symptoms. Effective treatment is required to control the intense inflammation observed after allergen exposure.



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Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer

Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer:

Abstract

Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival. Since 2013 nab-paclitaxel (paclitaxel-albumin-bound particles) became a new treatment option for patients with metastatic pancreatic cancer based on the results of MPACT trial. Moreover, encouraging activity in PDAC of the combination regimen of paclitaxel and carboplatin that is being widely used in other solid tumors has been reported recently. Biomarkers, including biomarkers predictive of taxane resistance, could allow individualized tailored therapy. BRCA mutation status could serve as predictor of better chemotherapy treatment outcome in PDAC. The present review summarizes the principal clinical trials evaluating the efficacy of taxanes both as monotherapy and in combination in view of the potential use in the treatment of PDAC.

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Letter: a simple out-patient faecal microbiota transplant technique

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Letter: oral low-dose methotrexate for collagenous colitis

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Letter: anti-TNF in steroid-dependent ulcerative colitis - are the available data enough?

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Letter: oral low-dose methotrexate for collagenous colitis – authors’ reply

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis – authors’ reply

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis

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Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer

Therapeutic potential of taxanes in the treatment of metastatic pancreatic cancer:

Abstract

Most patients with pancreatic ductal adenocarcinoma (PDAC) present with unresectable or metastatic disease with very poor prognosis. Chemotherapy is the primary treatment modality for patients with locally advanced and metastatic PDAC, but the efficacy of currently available regimens is limited. Taxanes are widely used in many primary cancers including breast, ovarian and lung cancers. The activity of combined regimen of taxanes plus nucleoside analogue or platinum derivate in terms of response rate ranges between 20 and 57 % in PDAC and may prolong overall survival. Since 2013 nab-paclitaxel (paclitaxel-albumin-bound particles) became a new treatment option for patients with metastatic pancreatic cancer based on the results of MPACT trial. Moreover, encouraging activity in PDAC of the combination regimen of paclitaxel and carboplatin that is being widely used in other solid tumors has been reported recently. Biomarkers, including biomarkers predictive of taxane resistance, could allow individualized tailored therapy. BRCA mutation status could serve as predictor of better chemotherapy treatment outcome in PDAC. The present review summarizes the principal clinical trials evaluating the efficacy of taxanes both as monotherapy and in combination in view of the potential use in the treatment of PDAC.

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Letter: a simple out-patient faecal microbiota transplant technique

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Letter: oral low-dose methotrexate for collagenous colitis

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Letter: anti-TNF in steroid-dependent ulcerative colitis - are the available data enough?

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Letter: oral low-dose methotrexate for collagenous colitis – authors’ reply

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis

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Letter: avoiding misconceptions about elimination diet for eosinophilic oesophagitis – authors’ reply

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Editors’ Declarations of Interest

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