Neurite outgrowth promotion in PC12 cells by 24(R)-ethyllophenol from Morus alba.

We examined the mechanism by which 24(R)-ethyllophenol (MAB28) isolated from the branches of Morus alba caused neurite outgrowth in rat pheochromocytoma cells (PC12). MAB28 significantly promoted neurite outgrowth to a similar degree as the positive control, nerve growth factor (NGF). After incubation with MAB28 in PC12 cells, phosphorylation of extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and cyclic AMP response element-binding protein was detected, but the time course of phosphorylation was different from that induced by NGF. The expression of chloride intracellular channel protein 3 (CLIC3) was significantly decreased by MAB28. 5-Nitro-2-(3-phenylpropylamino)-benzoic acid (NPPB), an outward rectifying chloride channel inhibitor, significantly promoted neurite outgrowth in PC12 cells. These data suggested that MAB28 could induce neurite outgrowth by downregulating CLIC3 expression.

QSAR model to predict Kp,uu,brain with a small dataset, incorporating predicted values of related parameter.

The unbound brain-to-plasma concentration ratio (Kp,uu,brain) is a parameter that indicates the extent of central nervous system penetration. Pharmaceutical companies build prediction models because many experiments are required to obtain Kp,uu,brain. However, the lack of data hinders the design of an accurate prediction model. To construct a quantitative structure-activity relationship (QSAR) model with a small dataset of Kp,uu,brain, we investigated whether the prediction accuracy could be improved by incorporating software-predicted brain penetration-related parameters (BPrPs) as explanatory variables for pharmacokinetic parameter prediction. We collected 88 compounds with experimental Kp,uu,brain from various official publications. Random forest was used as the machine learning model. First, we developed prediction models using only structural descriptors. Second, we verified the predictive accuracy of each model with the predicted values of BPrPs incorporated in various combinations. Third, the Kp,uu,brain of the in-house compounds was predicted and compared with the experimental values. The prediction accuracy was improved using five-fold cross-validation (RMSE = 0.455, r2 = 0.726) by incorporating BPrPs. Additionally, this model was verified using an external in-house dataset. The result suggested that using BPrPs as explanatory variables improve the prediction accuracy of the Kp,uu,brain QSAR model when the available number of datasets is small.

Recurrent respiratory epithelial adenomatoid hamartoma of the nasal cavity.

Respiratory epithelial adenomatoid hamartoma (REAH) refers to a rare entity characterized by excessive proliferation of the normal glandular elements of the respiratory epithelium present as mass lesions in various body sites. The pathophysiology of the disorder is still debated. The condition can closely mimic inverted papilloma, adenocarcinoma, and nasal polyposis clinically, radiologically, and pathologically. However, distinction from the above disorders is important in view of the excellent prognosis associated with complete excision of REAH. Recurrence is uncommon with complete excision, and a high-risk pathologic transformation is not expected with this lesion. We report a case of recurrent REAH managed with repeat surgical endoscopic excision. The patient is disease free 4 years after re-excision of the lesion.

Head and neck involvement with histoplasmosis; the great masquerader.

INTRODUCTION: Head and neck involvement with histoplasmosis usually occurs as a part of the disseminated illness. There are no pathognomic features of the upper aerodigestive tract involvement and the lesion may mimic a host of other conditions. The current report presents our experience with head and neck histoplasmosis in a non-endemic tertiary care center. MATERIALS AND METHODS: We present a case of disseminated histoplasmosis with oral symptoms and lesions as the chief complaints. A 10 years' retrospective institutional database search was undertaken to identify the patients with histoplasmosis affecting head and neck region treated at our institution. The demographic and treatment details of the patients were reviewed. RESULTS: In addition to the index patient, four more patients (two with gingivobuccal and one each with nasal and laryngeal histoplasmosis) were found. Out of the five patients, only one patient was found to have underlying immunosuppression. All of the patients were diagnosed with biopsy showing typical appearance of the intracellular organism. All the patients were satisfactorily treated with systemic antifungal treatment. CONCLUSION: Upper aerodigestive tract involvement with histoplasmosis can present as an intriguing clinical puzzle. A high index of suspicion is needed and biopsy is the gold standard for the diagnosis. Intravenous Liposomal Amphotericin B and oral Itraconazole are standard treatment agents of choice and are highly efficacious in achieving cure.

Bullet in tracheobronchial tree without lung contusion removed by fibreoptic bronchoscopy in two parts.

A person presented with multiple gunshot injury. Chest x-ray & CT whole body trauma protocol was done which showed multiples pellets of bullet in abdomen and one bullet in elbow according to entry wound. There was an entry wound without any bullet in left maxillofacial region however there was no exit wound. A bullet was noticed in tracheobronchial tree. There was no pneumothorax any signs of chest trauma or any pneumomediastinum. It is assumed that the bullet first hit the left cheek (maxilla) and lost its momentum. As the patient lost consciousness and had a fall leading to inhalation (aspiration) of bullet in the airway. As per ballistic experts it was basically a jacketed metallic bullet. As bullet moved in airway, the outer metallic core reached the trachea near carina and the soft metallic core slipped more distally to right main bronchus and bronchus intermedius. While inspection the outer metallic capsule was seen in trachea just above carina which was hollow and was gently removed with the help of foreign body forceps. The core was removed with dormia basket without any mucosal tear. The favorable outcome can be attributed as patient had no lung contusion or chest trauma and bullet was inhaled which was not very old. The evolution of bronchoscopy started with rigid one but the fibreoptic bronchoscopy (FOB) has revolutionized the pulmonary interventions. The FOB can be used with minimal traumas under local anesthesia resulting in markedly reduced morbidity and mortality.

Submandibular Duct Re-routing for Drooling in Neurologically Impaired Children.

Drooling is a challenging situation to manage especially in neurologically impaired pediatric population. Numerous surgical procedures have been described in literature but none of them is standardized. We evaluate the effectiveness of bilateral submandibular duct rerouting and sublingual gland excision in drooling paediatric patients. Prospective interventional study was conducted from November 2007 to September 2009 in twenty-eight pediatric patients with drooling who had failed conservative treatment modalities. Patients underwent bilateral submandibular duct transposition and sublingual gland excision. Patients were assessed pre-operatively, at 7, 30 and 90 days after surgery for drooling severity, frequency as per Thomas-Stonell and Greenberg classification and also number of bibs changed per day. Result was categorized using Wilkie and Brody criteria for assessing effectiveness of the surgery. Twenty-eight patients were successfully operated. All patients were followed-up for a duration of at least 3 months. The success rate achieved in term of control of drooling was 95.2 % at 3 months follow up. Statistically significant difference (p < 0.001) was noted in pre-operative and postoperative mean values for severity and frequency of drooling and also bibs/day. Transient, minor complications (n = 5/28, 17.8 %) were encountered following this surgical procedure. Bilateral submandibular duct rerouting and sublingual gland excision in drooling paediatric patients is a simple and effective surgery with minor operative morbidity. Concomitant sublingual gland excision bilaterally helps in reducing the incidence of ranula formation significantly.

Measurement and comparison of individual external doses of high-school students living in Japan, France, Poland and Belarus-the 'D-shuttle' project.

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter 'D-shuttle' for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the terrestrial background radiation level of other regions/countries.

Liver-Regenerative Transplantation: Regrow and Reset.

Liver transplantation, either a partial liver from a living or deceased donor or a whole liver from a deceased donor, is the only curative therapy for severe end-stage liver disease. Only one-third of those on the liver transplant waiting list will be transplanted, and the demand for livers is projected to increase 23% in the next 20 years. Consequently, organ availability is an absolute constraint on the number of liver transplants that can be performed. Regenerative therapies aim to enhance liver tissue repair and regeneration by any means available (cell repopulation, tissue engineering, biomaterials, proteins, small molecules, and genes). Recent experimental work suggests that liver repopulation and engineered liver tissue are best suited to the task if an unlimited availability of functional induced pluripotent stem (iPS)-derived liver cells can be achieved. The derivation of iPS cells by reprogramming cell fate has opened up new lines of investigation, for instance, the generation of iPS-derived xenogeneic organs or the possibility of simply inducing the liver to reprogram its own hepatocyte function after injury. We reviewed current knowledge about liver repopulation, generation of engineered livers and reprogramming of liver function. We also discussed the numerous barriers that have to be overcome for clinical implementation.

A study of voice profiles and acoustic signs in patients with Parkinson's disease in North India.

We aimed to study the voice profiles of patients with Parkinson's disease (PD) and correlate the profiles with disease severity. A total of 133 patients with PD were recruited. Patients were divided into two groups: Group 1 with a Unified Parkinson's Disease Rating Scale (UPDRS) score of ≤45; and Group 2 with a UPDRS >45. Speech was analyzed using the Indian Speech and Hearing Association (ISHA) articulation assessment and Vaghmi software. A total of 87 patients (65.41%) reported a history of speech problems. Examination revealed slow reading speed (64.7% of patients), hoarseness of voice (60.2%), articulatory defect (39.8%) and jerky speech (32.3%) as common abnormalities. Misarticulation was most often observed among the labial (42.1%), followed by lingual and palatal syllables. The ISHA articulation test demonstrated significant differences in mean numbers of words distorted (p<0.001) and intelligible speech (p=0.004) between patients with early and advanced PD. Vaghmi software analysis (Speech and Voice Systems, Bangalore, India) also revealed significant difference between the two groups in maximum phonation duration (p=0.034), inability to phonate (noiseless speech, Z; p=0.002) and the mean noise-to-noiseless speech (S/Z) ratio (p=0.006).

Insulinoma may mask the existence of Type 1 diabetes.

BACKGROUND: Insulinoma is a tumour of insulin-producing cells of the pancreas and is known to be one of the causes of hypoglycaemia. Usually, appropriate removal of the insulinoma results in normalization of blood glucose levels. However, we found novel cases of insulinoma, in which hyperglycaemia developed soon after resection of the insulinoma. CASE REPORT: We encountered two patients with repeated hypoglycaemia caused by insulinoma. Following removal of the insulinoma, unanticipated hyperglycaemia was observed in both patients. Thereafter, their blood tests revealed low levels of serum C-peptide and high titres of anti-glutamic acid decarboxylase antibody, indicating concomitant Type 1 diabetes. Indeed, histological examination of the resected specimen revealed that one patient showed insulitis in non-tumorous pancreatic tissue in which ß-cells had already disappeared. Moreover, inflammatory cells infiltrated the insulinoma, as if it were insulitis of Type 1 diabetes, suggesting the existence of anti-islet autoimmunity. CONCLUSION: These are first cases of insulinoma associated with underlying Type 1 diabetes. Physicians should be aware of the possibility that insulinoma may mask Type 1 diabetes, and measurement of anti-islet autoantibodies may be helpful to find underlying Type 1 diabetes, such as in these cases. It is pathologically interesting that the immune cell infiltration into insulinoma may be suggestive of anti-islet autoimmunity.

Changes in ventilatory function following surgery for bilateral abductor paralysis.

Management of bilateral vocal fold immobility continues to remain a challenge for the Otolaryngologist who attempts to create a balance between creation of an adequate airway and preservation of voice. The flow volume loop obtained by spirometry provides an ideal objective assessment tool to evaluate the results of surgery for this condition. Our experience in using peak inspiratory flow rate (PIFR) and forced inspiratory flow with 50% of vital capacity (FIF(50)) in the lung in assessing the results of surgery is described. Seventeen patients were included in the study. The surgical procedures performed included laser posterior cordectomy with partial arytenoidectomy, endoscopic arytenoidectomy and posterior cordectomy-Kashima's technique. Twelve out of 17 patients were successfully decannulated, a success rate of 70.6%. All patients except one showed an increase in mid-inspiratory flow rates and peak inspiratory flow rates. The mean increase in FIF(50) was 0.44 l/sec (52.6%) and the mean increase in PIFR was 0.41l/sec (39.77%). No statistically significant difference in improvement of inspiratory flow rates was observed between the three surgical procedures used in the study.

Post traumatic psuedoaneurysm of the lingual artery.

Post traumatic pseudoaneurysm is a well documented complication of vascular injuries which needs early diagnosis and early management otherwise there may be significant morbidity and mortality. We present a patient who had been operated elsewhere for a foreign body lodged in neck during splinter injury sustained while bursting a cracker. He presented to ENT department of our hospital with bleeding from the wound site. We are reporting this case because pseudoaneurysm of the lingual artery as such is very rare. We could not find any other reported case in available English literature. Moreover the treating ENT surgeons need to be sensitized to the presence of such an entity and hence avoid late complications.

A technique for the orientation of endoscopically resected laryngeal lesions.

Endoscopic resection is a widely accepted method of treating early laryngeal malignancies. Accurate histological assessment of resected laryngeal specimens can be difficult due to their small size and potential damage and distortion caused by standard orientation and processing techniques. A new technique is described which employs dehydrated cucumber to mount laryngeal specimens for orientation and processing. This technique is quick, easy, cheap and reliable, allowing accurate histological assessment of potentially malignant lesions. Better orientating and processing of laryngeal specimens can optimise treatment decisions based on histological results.

Unilateral pseudohypacusis in children.

Pseudohypacusis is a condition where there is hearing loss without any organic etiology. Though this condition has been reported long before, the literature exists mainly in the form of case reports. An interesting aspect of pseudohypacusis is of patients presenting with unilateral pseudohypacusis. In children, there often exist underlying psychological factors related to the occurrence of this condition. This condition is usually suspected when there is discrepancy in audiometric testing. The authors hereby report a child of unilateral pseudohypacusis presenting with psychological stressors, along with an overview of the management of such conditions.

HPV16 E6-mediated stabilization of ErbB2 in neoplastic transformation of human cervical keratinocytes.

Whether ErbB2 receptor tyrosine kinase contributes to cervical cancer is controversial. We have examined the effects of E6 and E7 genes of human papillomaviruses type 16 (HPV-16) on ErbB2 expression in primary human cervical keratinocytes (HCK) immortalized with hTERT (HCK1T). In E6-positive cells (HCK1T-E6 and HCK1T-E6E7), ErbB2 expression levels increased with the cell density. HCK1T-E6E7 showed impaired contact inhibition and anchorage-independent growth in soft agar which were abrogated with introduction of ErbB2-specific short hairpin RNA (shRNA) or an ErbB2 specific inhibitor AG825. Furthermore, increased ErbB2 expression was also observed in HPV16 positive cervical cancer cell lines and this was diminished by introduction of HPV16E6- or E6AP-shRNA. At post-confluence cell densities, ErbB2 protein was stabilized in the presence of E6 whereas increased ErbB2 expression was not obvious with E6 mutants incapable of degrading p53. Furthermore, introduction of p53-shRNA to HCK1T resulted in increased ErbB2 protein stability, indicating possible ErbB2 regulation through p53. Finally, we showed that tumor formation of ErbB2-shRNA introduced SiHa cells were almost abolished. Taken together, these data indicate an important role of ErbB2 regulation by HPV16 E6 in oncogenic transformation of human cervical keratinocytes.

Management protocols of Allergic Fungal Sinusitis.

Controversy surrounds the appropriate surgical approach and the appropriate medical therapy for Allergic Fungal Sinusitis. The present prospective study aims to assess the impact of these factors on the treatment outcome of Allergic Fungal Sinusitis. In the present study 34 cases with AFS were randomized into one of 3 methods of post operative therapy i.e. systemic itraconazole (group A, n=11), topical steroids (group B, n=12) and nasal alkaline douches only (group C, n=11). Outcome was assessed at 6 months post-operative by the Kupferberg grading system for assessment of nasal and sinus mucosa. Grade '3' mucosal disease was defined as recurrence.Complete pre-operative opacification of sphenoid and frontal sinus was a predictor of poorer outcome. Postoperative systemic itraconazole therapy demonstrated a trend towards a better outcome but was not statistically significant. Larger trials are required to conclusively evaluate the merit of various post-operative treatment regimens for AFS.

Validation of the modified Berlin questionnaire to identify patients at risk for the obstructive sleep apnoea syndrome.

BACKGROUND & OBJECTIVES: Awareness regarding obstructive sleep apnoea (OSA) among general public as well as practicing physicians is low in India. The present study was undertaken to test the utility of modified Berlin questionnaire for risk categorization of OSA in Indian setting. METHODS: The modified Berlin questionnaire was administered in 180 middle aged adults (of 320 screened), of whom, 104 underwent overnight polysomnograhy, in a cross-sectional study at a tertiary care, referral center in north India. Questionnaire addressed the presence of frequency of snoring, wake time sleepiness, fatigue, obesity and hypertension. Subjects with persistent and frequent symptoms in any two of these three domains were considered in high risk category for obstructive sleep apnoea. Overnight polysomnograhy was performed to measure apnoea and hypopnoea index (AHI). RESULTS: Questions about the symptoms demonstrated internal consistency (Cronbach alpha correlations 0.92-0.96). Of the 180 respondents to the screening questions, 80 were in the high risk and the rest were in low risk group. For 104 subjects who underwent polysomnograhy, risk grouping was useful in prediction of AHI. High risk category predicted an AHI >5 with a sensitivity of 86 per cent, specificity of 95 per cent, positive and negative predictive values of 96 and 82 per cent respectively. These results were comparable to Berlin questionnaire study done in the western population for validation. INTERPRETATION & CONCLUSION: On the basis of the findings of present study it is concluded that administration of modified Berlin questionnaire prior to a polysomnography study can identify high risk subjects and can thus avoid unnecessary polysomnography studies especially in resource-limited settings. To identify subjects at risk for OSA syndrome in general population, this questionnaire can be applied. However, the findings of the present study need to be confirmed further in a large number of subjects in a community-based setting.

STAT3 activation via interleukin 6 trans-signalling contributes to ileitis in SAMP1/Yit mice.

BACKGROUND AND AIMS: SAMP1/Yit mice spontaneously develops intestinal inflammation. Previously, we demonstrated that the signal transducer and activator of transcription (STAT)-3/suppressor of cytokine signalling (SOCS)-3 pathway is pivotal in human inflammatory bowel disease. In our studies in SAMP1/Yit mice, the aim was to investigate whether STAT3 activation contributes to ileitis and to examine the therapeutic effects of this signal blockade. METHODS: Intestinal expression of phospho-STAT3 in SAMP1/Yit mice and control AKR/J mice was examined by western blotting and immunohistochemistry. SOCS3 and interleukin 6 (IL-6) mRNA were determined by northern blotting and reverse transcription-polymerase chain reaction, respectively. We also examined the effects of intravenously injected hyper-IL-6, an IL-6/soluble IL-6 receptor fusion protein, and of soluble gp130-Fc, a specific inhibitor of soluble IL-6 receptor signalling, on STAT3 phosphorylation and disease severity in SAMP1/Yit mice. RESULTS: Phospho-STAT3 was expressed strongly during the disease course in SAMP1/Yit mice but only transiently in AKR/J mice. Phospho-STAT3 was localised to epithelial and mononuclear cells in the diseased intestine of SAMP1/Yit mice. SOCS3 as well as IL-6 mRNAs were expressed in affected intestine. Administration of hyper-IL-6 caused disease exacerbation and enhancement of STAT3 phosphorylation. In contrast, soluble gp130-Fc administration ameliorated the disease and suppressed STAT3 phosphorylation. CONCLUSION: STAT3 signalling is critical in the development of intestinal inflammation in SAMP1/Yit mice. Blockade of this signalling pathway by soluble gp130-Fc may have therapeutic effects in inflammatory bowel disease.

Prediction of obstructive sleep apnea in patients presenting to a tertiary care center.

The objective of this prospective observational clinical study is to derive and validate a diagnostic model for prediction of obstructive sleep apnea (OSA) in subjects presenting with non-sleep-related complaints in a tertiary care center in north India. We included 102 subjects (group I, range 31-70 years) presenting to the hospital with non-sleep-related complaints. None of the subjects had any significant comorbid illness such as respiratory or congestive cardiac failure. All subjects underwent detailed evaluation including polysomnography (PSG). Various parameters were compared between the cases (apnea-hypopnea index, AHI > or =15/h) and controls (AHI <15/h). Using multivariate logistic regression analysis, a diagnostic model for prediction of OSA was derived. Subsequently, using similar selection criteria, 104 subjects (group II, range 32-68 years) were included for validation of the newly derived diagnostic model. Body mass index [BMI; OR (95% CI), 1.14(1.1-1.2)], male gender 5.0(1.4-27.1), relative-reported snoring index (SI) 2.8(1.7-5.0), and choking index (ChI) 8.1(1.4-46.5) were significant, independent predictors of OSA. Diagnostic model was computed as score = [1.61 x (gender)] + [1.01 x (S1)] + [2.09 x (ChI)] + [0.1 x (BMI)] where, gender: 0 = female, 1 = male and SI, ChI, BMI are actual values. The diagnostic model had an area under the receiver operator characteristics curve of 89.6%. A cutoff of 4.3 for the score was associated with sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of 91.3, 68.5, 70.5, and 92.3%, respectively. Misclassification rate with the application of the diagnostic model on group II subjects was 13.5% (14/104). Sensitivity, specificity, PPV, and NPV of the model for predicting OSA in this group were 82, 90.7, 89.1, and 84.5%, respectively. BMI, male gender, SI, and ChI are independent predictors of OSA. Diagnostic model derived from these parameters is useful for predicting presence of OSA and screening subjects for PSG.