Bioequivalence of a new coated 15 mg primaquine formulation for malaria elimination.

BACKGROUND: With only one 15 mg primaquine tablet registered by a stringent regulatory authority and marketed, more quality-assured primaquine is needed to meet the demands of malaria elimination. METHODS: A classic, two sequence, crossover study, with a 10-day wash out period, of 15 mg of IPCA-produced test primaquine tablets and 15 mg of Sanofi reference primaquine tablets was conducted. Healthy volunteers, aged 18-45 years, without glucose-6-phosphate dehydrogenase deficiency, a baseline haemoglobin ≥ 11 g/dL, creatinine clearance ≥ 70 mL/min/1.73 ms, and body mass index of 18.5-30 kg/m2 were randomized to either test or reference primaquine, administered on an empty stomach with 240 mL of water. Plasma primaquine and carboxyprimaquine concentrations were measured at baseline, then 0.25, 0.5, 0.75, 1.0, 1.25, 1.5, 1.75, 2.0, 2.333, 2.667, 3.0, 3.5, 4.0, 4.5, 5.0, 5.5, 6.0, 8.0, 10.0, 12.0, 16.0, 24.0, 36.0, 48.0 and 72.0 h by liquid chromatography coupled to tandem mass spectrometry. Primaquine pharmacokinetic profiles were evaluated by non-compartmental analysis and bioequivalence concluded if the 90% confidence intervals (CI) of geometric mean (GM) ratios of test vs. reference formulation for the peak concentrations (Cmax) and area under the drug concentration-time (AUC0-t) were within 80.00 to 125.00%. RESULTS: 47 of 50 volunteers, median age 33 years, completed both dosing rounds and were included in the bioequivalence analysis. For primaquine, GM Cmax values for test and reference formulations were 62.12 vs. 59.63 ng/mL, resulting in a GM ratio (90% CI) of 104.17% (96.92-111.96%); the corresponding GM AUC0-t values were 596.56 vs. 564.09 ngxh/mL, for a GM ratio of 105.76% (99.76-112.08%). Intra-subject coefficient of variation was 20.99% for Cmax and 16.83% for AUC0-t. Median clearances and volumes of distribution were similar between the test and reference products: 24.6 vs. 25.2 L/h, 189.4 vs. 191.0 L, whilst the median half-lives were the same, 5.2 h. CONCLUSION: IPCA primaquine was bioequivalent to the Sanofi primaquine. This opens the door to prequalification, registration in malaria endemic countries, and programmatic use for malaria elimination. Trial registration The trial registration reference is ISRCTN 54640699.

Survival rate of dental implant placed using various maxillary sinus floor elevation techniques: A systematic review and meta-analysis.

Aim: The aim of this systematic review is to evaluate the survival rate of dental implant placed using different maxillary sinus floor elevation techniques. Setting and Design: PRISMA guidelines were used for this systematic review and meta-analysis. Materials and Methods: Relevant articles were searched from Medline, PubMed, Google Scholar, ScienceDirect, and Cochrane trials. Articles published in English language were selected. Hand search was further conducted. For risk of bias, two tools were used, i.e., Cochrane tool for randomized controlled trials (RCTs) and new castle Ottawa quality assessment tool for non-RCTs. Statistical Analysis: For statistical meta-analysis RevMan 5.4 software was used. Results: Seventeen studies were finalized. All studies were included in the meta-analysis to check the implant survival rate. There is no statistical difference between direct and indirect techniques, and forest plot was derived for direct approach (P = 0.688, 95% confidence interval [CI] 0.9691) and for indirect approach (P = 0.686 and 95% CI 0.970). Conclusion: There is no statistically significant difference in the survival rate of implant placed using direct or indirect sinus lift approach procedures. Hence, the technique is selected as per the indications given for each direct and indirect procedure.

Clear cell variant of oral squamous cell carcinoma: case report and review.

The clear cell variant of Oral Squamous Cell Carcinoma (OSCC) is an uncommon histological variant. Kuo first discovered it in the skin, and Frazier et al. found it in the oral cavity. We know of only nine cases of clear cell variant of OSCC reported in the literature till now. The present case is in a 60-year-old male patient with an ulcer on the left posterolateral border of the tongue. The patient had a history of chewing tobacco for 22 years. Clinical examination showed features of malignant ulcer associated with pain and discomfort. Histopathological examination revealed sheets and islands of atypical epithelial cells with clear cytoplasm, nuclear and cellular pleomorphism, and few keratin pearls in the connective tissue suggesting OSCC. Various special stains were performed to identify clear cells. Periodic Acid Schiff-Diastase (PAS-D) and Mucicarmine stains showed positive and negative reactions in clear cells, respectively. Immunohistochemical (IHC) analysis for cytokeratin (AE1/AE3) showed diffuse positivity in clear cells and other epithelial cells. Based on special stains and IHC markers, we confirmed the diagnosis as a clear cell variant of OSCC. This variant is rare and presents diagnostic challenges. It is said to be aggressive in nature. More such cases should be reported to understand its biological behavior and prognosis.

Intranasal delivery of insulin by self-emulsified nanoemulsion system: In vitro and in vivo studies.

The main objective of this research was to develop a self-emulsified nanoemulsion (SEN) dosage form of insulin where insulin is loaded into the lipid phase of the nanoemulsion for enhanced absorption through intranasal delivery. When loaded into the lipid droplets (oil phase), insulin can be protected from enzymatic degradation, can penetrate through the mucus gel barrier in a comparatively effective manner and can be absorbed through transcellular permeation along with paracellular route. To incorporate lipophilicity to insulin molecule, Ins-SPC (Soy-L-α-phosphatidylcholine) complex was prepared by solid dispersion method to load insulin into the oil phase. The cytotoxicity of SPC and the developed nanoemulsions was tested on the human nasal epithelial cells in vitro. An optimized formulation with high loading of insulin and low in vitro cytotoxicity was developed and characterized. To predict the absorption of insulin through nasal mucosa in vivo by the nanoemulsion system, the insulin-loaded SEN along with controls was tested for the transport through human nasal epithelial cell monolayer in vitro. The insulin-loaded SEN significantly (p < 0.01) enhanced the permeation of insulin by three times as compared to the insulin solution. The in vivo absorption of insulin after intranasal delivery of the insulin-loaded SEN was evaluated in anesthetized rats. The results show that the Cmax (maximum plasma concentration) and the bioavailability (relative to the subcutaneous delivery) of the insulin-loaded SEN was 255.9 µU/ml and 68 %, respectively, while the intranasal delivery of the insulin solution resulted in only 5.8 µU/ml of Cmax and 5% of relative bioavailability. Intranasal delivery of 3.6 IU/kg insulin-loaded SEN decreased the plasma glucose level remarkably, achieving a maximum reduction of 70%, and the glucose reduction activity lasted for the whole experimental period of 4 h. Histological examination of the nasal mucosa showed no apparent signs of toxicity at the site of administration after single dose of the insulin-loaded SEN. These results demonstrate that the insulin-loaded SEN significantly enhanced insulin absorption through intranasal delivery, indicating that the developed nanoemulsion system offers a favorable approach for intranasal delivery of insulin.

Clear cell variant of oral squamous cell carcinoma: case report and review

Abstract The clear cell variant of Oral Squamous Cell Carcinoma (OSCC) is an uncommon histological variant. Kuo first discovered it in the skin, and Frazier et al. found it in the oral cavity. We know of only nine cases of clear cell variant of OSCC reported in the literature till now. The present case is in a 60-year-old male patient with an ulcer on the left posterolateral border of the tongue. The patient had a history of chewing tobacco for 22 years. Clinical examination showed features of malignant ulcer associated with pain and discomfort. Histopathological examination revealed sheets and islands of atypical epithelial cells with clear cytoplasm, nuclear and cellular pleomorphism, and few keratin pearls in the connective tissue suggesting OSCC. Various special stains were performed to identify clear cells. Periodic Acid Schiff-Diastase (PAS-D) and Mucicarmine stains showed positive and negative reactions in clear cells, respectively. Immunohistochemical (IHC) analysis for cytokeratin (AE1/AE3) showed diffuse positivity in clear cells and other epithelial cells. Based on special stains and IHC markers, we confirmed the diagnosis as a clear cell variant of OSCC. This variant is rare and presents diagnostic challenges. It is said to be aggressive in nature. More such cases should be reported to understand its biological behavior and prognosis.

Comparative evaluation of occlusal splint therapy and muscle energy technique in the management of temporomandibular disorders: A randomized controlled clinical trial.

Background: Contradicting evidence regarding the effects of occlusal splint therapy in the management of Temporomandibular disorder (TMD) and promising results shown by muscle energy technique. Aim: To determine and compare the effects of occlusal splint therapy, muscle energy technique, and combined treatment with education for self-management and counseling in the management of TMD. Study Design and Settings: Randomized clinical trial. Methodology: A total of 160 participants diagnosed with TMD according to Diagnostic Criteria/TMD axis I were randomly allocated into four treatment groups with equal allocation ratio using random numbers table. The main inclusion criteria were the presence of pain in the preauricular area, TMJ and/or muscles of mastication and maximum mouth opening <40 mm. Group A participants received muscle energy technique, Group B participants received occlusal splint therapy, Group C participants received combined treatment, and Group D participants received education for self-management and counseling (control). Control group treatment was provided to all the trial participants. Statistical Analysis: Intragroup comparison was made using Friedman test and Wilcoxon test while intergroup comparison was done using Kruskal-Wallis test and Mann-Whitney U test. Results: Intensity of pain on a visual analog scale and maximum mouth opening were measured at baseline, at 1 week, at 2 weeks, at 1 month, and after 3 months. Conclusion: Muscle energy technique, occlusal splint therapy and combined treatment significantly reduce pain compared to controls and muscle energy and combined treatment are superior to other groups for mouth opening improvements in patients with TMD.

Protection of Protein Drugs by Self-Emulsified Nanoemulsion Against Proteolysis.

The present study aimed to develop a self-emulsified nanoemulsion for salmon calcitonin (sCT) for non-invasive delivery. Hydrophobic ion pairing method was used to form hydrophobic complex of sCT with 4 counter ions (oleate, deoxycholate, docusate and tripolyphosphate). The partition coefficient and dissociation of the complexes in water of various pH were investigated. The complex-loaded nanoemulsions were characterized for droplet size, leakage of sCT from the droplets, and protection of sCT from enzymatic degradation. The results show that all the counter ions could form complexes with sCT with a complexation efficiency about 95% at pH 8.0. The complexes significantly increased the partition coefficient of sCT. The dissociation of the complexes in water was pH-dependent. At pH 6.8 and 7.4, the dissociation was negligible. At pH 1.0, the dissociation was 71%, 8%, 37% and 50% for sCT-polyphosphate, sCT-docusate, sCT-oleate and sCT-deoxycholate, respectively. The developed nanoemulsions had a size in the range of 27-62 nm. The leakage of sCT from the nanodroplets into the aqueous phase depended on the lipophilicity of the counter ions: 60%, 56%, and 24% leakage for sCT-docusate, sCT-oleate and sCT-deoxycholate, respectively. The nanoemulsion protected sCT from enzyme degradation when loaded inside the droplets, but not the leaked sCT.

FITC labeling of human insulin and transport of FITC-insulin conjugates through MDCK cell monolayer / 药物分析学报

Fluorescein isothiocyanate-labeled insulin (FITC-insulin) has been widely used for bioanalytical appli-cations. Due to the high cost of commercial FITC-insulin and tedious labeling procedures described in the literature, there is still a need to develop a cost effective, reliable and quick labeling method for insulin. The purpose of the present work was to develop a quick and affordable method for FITC labeling of human insulin and to determine the effect of different conjugations of FITC to human insulin on its permeability through the MDCK cell monolayer. FITC labeling of insulin gives mono-, di-or tri-conjugates depending on the reaction time and the molar ratio of FITC:insulin. Mono-conjugate with unlabeled insulin, mixture of di-and tri-conjugate, and tri-conjugate with very little amount of di-conjugate were synthesized in less than 4 h. Degree of conjugation had an effect on the permeability of insulin through the MDCK cell monolayer. Mono-conjugate had higher permeability than the unlabeled insulin due to increase in partition coefficient. However, tri-conjugate showed lower permeability than the unlabeled insulin due to the increase in molecular weight.

FITC labeling of human insulin and transport of FITC-insulin conjugates through MDCK cell monolayer.

Fluorescein isothiocyanate-labeled insulin (FITC-insulin) has been widely used for bioanalytical applications. Due to the high cost of commercial FITC-insulin and tedious labeling procedures described in the literature, there is still a need to develop a cost effective, reliable and quick labeling method for insulin. The purpose of the present work was to develop a quick and affordable method for FITC labeling of human insulin and to determine the effect of different conjugations of FITC to human insulin on its permeability through the MDCK cell monolayer. FITC labeling of insulin gives mono-, di- or tri-conjugates depending on the reaction time and the molar ratio of FITC:insulin. Mono-conjugate with unlabeled insulin, mixture of di- and tri-conjugate, and tri-conjugate with very little amount of di-conjugate were synthesized in less than 4 h. Degree of conjugation had an effect on the permeability of insulin through the MDCK cell monolayer. Mono-conjugate had higher permeability than the unlabeled insulin due to increase in partition coefficient. However, tri-conjugate showed lower permeability than the unlabeled insulin due to the increase in molecular weight.

Fibrolipoma on a Child's Lip: A Rare Clinical Finding.

Lipoma is very common benign tumor of adipose tissue, but its presence in the oral cavity is rare. Fibrolipoma is a histological variant of lipoma that affects the buccal mucosa and nasal septum in the orofacial region and causes functional and cosmetic issues. However, this lesion has not been reported on the upper lip and may be confused with other soft tissue lesions of children. Hence, accurate histopathological examination of lipomas is important for a correct treatment plan. The purpose of this report is to describe the case of an 11-year-old boy with fibrolipoma of the upper lip.

Various bio-mechanical factors affecting heat generation during osteotomy preparation: A systematic review.

BACKGROUND: As implant site preparation and bone are critical precursors to primary healing, thermal and mechanical damage to the bone must be minimized during the preparation of the implant site. Moreover, excessively traumatic surgery can adversely affect the maturation of bone tissue at the bone/implant interface and consequently diminish the predictability of osseointegration. So, this study was carried out to evaluate the various biological and mechanical factors responsible for heat generation during osteotomy site preparation to reduce the same for successful osseointegration of dental implants. STUDY DESIGN: A broad search of the dental literature in PubMed added by manual search was performed for articles published between 1992 and December 2015. Various bio-mechanical factors related to dental implant osteotomy preparation such as dental implant drill designs/material/wear, drilling methods, type of irrigation, and bone quality were reviewed. Titles and abstracts were screened and articles which fulfilled the inclusion criteria were selected for a full-text reading. RESULTS: The initial database search yielded 123 titles, of which 59 titles were discarded after reading the titles and abstracts, 30 articles were again excluded based on inclusion and exclusion criteria, and finally 34 articles were selected for data extraction. Many biological and mechanical factors responsible for heat generation were found. CONCLUSION: Literatures of this review study have indicated that there are various bio-mechanical reasons, which affect the temperature rise during osteotomy and suggest that the amount of heat generation is a multifactorial in nature and it should be minimized for better primary healing of the implant site.

Restoring Faculty Vitality in Academic Medicine When Burnout Threatens.

Increasing rates of burnout-with accompanying stress and lack of engagement-among faculty, residents, students, and practicing physicians have caused alarm in academic medicine. Central to the debate among academic medicine's stakeholders are oft-competing issues of social accountability; cost containment; effectiveness of academic medicine's institutions; faculty recruitment, retention, and satisfaction; increasing expectations for faculty; and mission-based productivity.The authors propose that understanding and fostering what contributes to faculty and institutional vitality is central to preventing burnout during times of change. They first look at faculty vitality and how it is threatened by burnout, to provide a framework for a greater understanding of faculty well-being. Then they draw on higher education literature to determine how vitality is defined in academic settings and what factors affect faculty vitality within the context of academic medicine. Next, they propose a model to explain and examine faculty vitality in academic medicine, followed by a discussion of the need for a greater understanding of faculty vitality. Finally, the authors offer conclusions and propose future directions to promote faculty vitality.The authors encourage institutional decision makers and other stakeholders to focus particular attention on the evolving expectations for faculty, the risk of extensive faculty burnout, and the opportunity to reduce burnout by improving the vitality and resilience of these talented and crucial contributors. Faculty vitality, as defined by the institution, has a critical role in ensuring future institutional successes and the capacity for faculty to thrive in a complex health care economy.

Effectiveness of hyperbaric oxygen therapy in irradiated maxillofacial dental implant patients: A systematic review with meta-analysis.

The significantly higher implant failure rates in maxillofacial patients, undergoing radiotherapy, might be caused by the long-term effects of reduced vascularization compromising the implantation site. An extensive preclinical animal literature and a multitude of clinical reports suggest the use of hyperbaric oxygen (HBO) therapy as it can improve the tissue vascularity. Hence, it may increase the implant survival rate by enhancing osseointegration process in such patients. The objective of this systematic review was to investigate the effectiveness of HBO therapy on dental implant survival rate in irradiated maxillofacial patients who require prosthodontic rehabilitation. An electronic search without time restrictions was undertaken in April 2016 using databases: PubMed, Google Scholar, and the Cochrane Oral Health Group Trials Register. We also tried to contact the manufacturers and researchers in the field for necessary details. Clinical human studies, on irradiated maxillofacial dental implant patients, including randomized controlled trials (RCTs), prospective controlled trials, retrospective studies, and preliminary reports were included in the study. Data collection was carried out by two of the authors' independently. The titles and abstracts of all reports were screened for the study design and type of reported intervention; all the duplicates were removed. The data search yielded 62 titles, out of which 14 articles were selected for the study by the article filtration criteria: Title/abstract/full text. Data which were extracted by two authors with any disagreement were resolved by the third author, and a meta-analysis was done using binary random-effect model. The results show decreased implant failure rate in HBO group (9.21%) compared to non-HBO group (22.44%). The potential limitations of this study are amount of radiation doses used, period lasting from radiotherapy to the placement of the implants, and follow-up period which varies for every subject of the included study, which can affect the treatment outcome. Although there are many sensitive articles published about HBO, including a number of review papers, RCTs are still lacking. According to the statistical analysis, it can be concluded that preventive HBO therapy can reduce the risk of implant failures in irradiated patients by 1.21 (relative risk) with 95% confidence interval (P < 0.001). Hence, HBO can be the effective treatment protocol for the implant treatment in irradiated maxillofacial patients.

Evaluation of flexural strength and color stability of different denture base materials including flexible material after using different denture cleansers.

AIMS: Present study aimed at evaluating the colour stability and flexural strength of flexible denture base materials (Valplast) and Polymethyl methacrylate (PMMA) denture base material (Meliodent) processed by two different methods (Injection moulding and compression moulding) after immersing them in three different denture cleansers with acidic, basic and neutral PH. METHODS AND MATERIALS: Total 120 specimens (65 × 10 × 3 mm3), 40 specimens of each material (Valplast, Meliodent compression moulding and injection moulding) were immersed in denture cleansers having different PH; Valclean (Acidic), Clinsodent (Basic) and Polident (Neutral) as well as Distilled Water. Color changes were measured with a spectrophotometer after 1 month, 3 months and 6 months of immersion cycle. A flexural 3-point bending test was carried out by using an Instron universal testing machine after 6 months of soaking. Data were analyzed using SPSS software. RESULTS: Maximum effect on colour stability was noted with Clinsodent followed by Valclean. Least color changes were observed after immersion in Polident. Colour difference was increased significantly as the immersion time increased. For both Meliodent and Nylon resins, statistically significant change in flexural strength occurred with immersion in all denture cleansers. Clinsodent has greater effect as compared to Valclean and Polident. CONCLUSIONS: Polident and Valclean can be safely used as denture cleanser for both nylon and acrylic resin denture base materials as far as colour stability and flexural strength both are concerned.

Consensus Guidelines for Practical Competencies in Anatomic Pathology and Laboratory Medicine for the Undifferentiated Graduating Medical Student.

The practice of pathology is not generally addressed in the undergraduate medical school curriculum. It is desirable to develop practical pathology competencies in the fields of anatomic pathology and laboratory medicine for every graduating medical student to facilitate (1) instruction in effective utilization of these services for optimal patient care, (2) recognition of the role of pathologists and laboratory scientists as consultants, and (3) exposure to the field of pathology as a possible career choice. A national committee was formed, including experts in anatomic pathology and/or laboratory medicine and in medical education. Suggested practical pathology competencies were developed in 9 subspecialty domains based on literature review and committee deliberations. The competencies were distributed in the form of a survey in late 2012 through the first half of 2013 to the medical education community for feedback, which was subjected to quantitative and qualitative analysis. An approval rate of ≥80% constituted consensus for adoption of a competency, with additional inclusions/modifications considered following committee review of comments. The survey included 79 proposed competencies. There were 265 respondents, the majority being pathologists. Seventy-two percent (57 of 79) of the competencies were approved by ≥80% of respondents. Numerous comments (N = 503) provided a robust resource for qualitative analysis. Following committee review, 71 competencies (including 27 modified and 3 new competencies) were considered to be essential for undifferentiated graduating medical students. Guidelines for practical pathology competencies have been developed, with the hope that they will be implemented in undergraduate medical school curricula.

Isolated Candida infection of the lung.

Candida pneumonia is a rare infection of the lungs, with the majority of cases occurring secondary to hematological dissemination of Candida organisms from a distant site, usually the gastrointestinal tract or skin. We report a case of a 77-year-old male who is life-long smoker with a history of rheumatoid arthritis and polymyalgia rheumatica, but did not take immunosuppressants for those conditions. Here, we present an extremely rare case of isolated pulmonary parenchymal Candida infection in the form pulmonary nodules without evidence of systemic disease which has only been described in a few previous reports.

Prosthetic status and prosthetic need among the patients attending various dental institutes of ahmedabad and gandhinagar district, gujarat.

The oral health being an integral part for the healthy living, necessity of disability limitation and rehabilitation in oral health has taken a paramount role. To assess the prosthetic status and to evaluate the prosthetic needs of the patients attending various institutes of Ahmedabad and Gandhinagar district. A total of 510 (264 males and 246 females) subjects at various dental institutes were examined in the study. A survey proforma was prepared with the help of WHO oral health assessment form (1997). Prosthetic status and prosthetic treatment need was recorded. Out of 510, any type of Edentulousness was 322 (63 %). Among them, 254 (49.8 %) were partially edentulous while 68 (13.3 %) were completely edentulous. Only 69 (13 %) were having any prosthesis in upper arch while only 80 (16 %) were having any prosthesis in lower arch. Need for any type of prosthesis in upper and lower arch was 55 and 60 % in males and females, respectively. In lower social class group need of prosthesis in upper and lower arch was 62 and 63 %, respectively. It was found that prosthetic status and prosthetic treatment need increased with increase in age. Steps should be taken to overcome this disparity and more emphasis should be given to meet the felt need of the people through government and non government organizations to improve the oral health. The unmet prosthetic treatment need should be met to rehabilitate needy people so that their disability may be limited.