Shaping subcellular tubes through vesicle trafficking: Common and distinct pathways.

Cells with subcellular lumens form some of the most miniature tubes in the tubular organs of animals. These are often crucial components of the system, executing functions at remote body locations. Unlike tubes formed by intercellular or autocellular junctions, the cells with junctionless subcellular lumens face unique challenges in modifying the cell shape and plasma membrane organization to incorporate a membrane-bound tube within, often associated with dramatic cellular growth and extensions. Results in the recent years have shown that membrane dynamics, including both the primary delivery and recycling, is crucial in providing the cell with the flexibility to face these challenges. A significant portion of this information has come from two in vivo invertebrate models; the Drosophila tracheal terminal cells and the C. elegans excretory cell. This review focuses on the data obtained from these systems in the recent past about how trafficking pathways influence subcellular tube and branching morphogenesis. Given that such tubes occur in vertebrate vasculature, these insights are relevant to human health, and we contrast our conclusions with the less understood subcellular tubes of angiogenesis.

Single Sitting Surgery for Concomitant Hydatid Cyst of Lung and Liver: A Case Report.

Hydatid disease is one of the diseases that have been discovered in the ancient times. Liver and lung are the most commonly affected organs, though it can involve any organs. Hydatid disease involving both the liver and the lung is reported about 10% of the cases. Here we report a case of 34 year old male presented with upper abdominal pain and intermittent fever for 3 months admitted in October 2016. His chest radiograph and computed tomography scan revealed large cystic lesion at right lung and another similar large lesion in the right lobe of liver. Echinococcus antibody was found positive. We treated him surgically. Histopathology reports confirmed concomitant hydatid cyst of both the lung and the liver.

Solid Pseudopapillary Tumor of the Pancreas: A Case Report.

Solid pseudopapillary tumors (SPT) of the pancreas are rare neoplasms of the pancreas accounting for only 1-2% of all pancreatic neoplasms, often detected initially on imaging. Its histogenesis is still uncertain and it has a low-grade malignant potential but excellent post-surgical curative rates and rare metastasis. Pathological and/or cytological evaluation still remains the gold standard in reaching a definitive diagnosis. It occurs most commonly in young females. We report a case of solid pseudopapillary tumor in the head of the pancreas in a 20 years old female admitted in Bangabandhu Sheikh Mujib Medical University (BSMMU), Dhaka, Bangladesh on 5th December 2015. Whipple's operation was done as a definitive treatment.

Hormonal Changes in Intracranial Hemorrhage.

INTRODUCTION: The purpose of this study was to investigate the changes of serum ACTH and Thyroid hormone level in the acute phase of ICH. METHODS: Sixty patients with spontaneous ICH were assessed regarding hormonal changes by measuring ACTH and Thyroid hormone level. The relationships of hormone concentrations to clinical and radiological parameters were evaluated at hospital admission (t0), 5 days (t1) and 10 days (t2). The results were statistically analyzed. RESULTS: ACTH, TSH, Thyroxine, and free Thyroxine were not significantly different among the three time periods (P > 0.05), while Triiodothyronine (T3) and free Triiodothyronine (FT3) were significantly different (P < 0.05). T3 and FT3 were not significantly different among patients with hemorrhage of different locations (P>0.05). There were significant negative correlations between T3 and FT3 with volume of ICH (r=-0.63 and r=-0.25) and there were positive correlations between T3 and FT3 with GCS (r=0.63 and r=0.37) respectively on admission day (p <0.05). CONCLUSIONS: Hormonal secretion patterns is associated with the severity of ICH. This is an important index to evaluate the disease severity and prognosis.

CDK4 in lung, and head and neck cancers in old age: evaluation as a biomarker

Background. Cyclin dependent kinases (CDK) are key factors in promoting the initiation and development of tumors. These kinases are important for maintenance of mitochondrial biogenesis and imbalance in their expression in old age may lead to the oxidative stress. Lung cancer (LC), and head and neck squamous cell carcinoma (HNSCC) are two very prominent cancers in older Indians. Both the cancers are showing increasing trend in older population. The present study assessed serum concentration of one of the kinases; CDK4 in older LC and HNSCC patients. Methods. The study included 100 subjects each of LC and HNSCC; and older subjects without cancer or any major health problems as controls. Serum CDK4 concentration was estimated using real-time label-free Surface plasmon resonance (SPR) and was verified by western blot. Results. Significant elevation in serum CDK4 was observed in cases with LC and HNSCC compared to controls. HNSCC patients with higher CDK4 expression had distinctly shorter survival than patients with comparatively lower CDK4 expression. No such difference was observed in LC patients. The germ line mutation study of this gene in Exon-2 was performed and none was observed among cases and controls. Conclusion. It can be concluded that older patients with HNSCC and lung cancer have raised serums CDK4 levels, which has the potential to emerge as a biomarker in clinical practice (AU)

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N-terminal or signal peptide sequence engineering prevents truncation of human monoclonal antibody light chains.

Monoclonal antibodies (mAbs) contain short N-terminal signal peptides on each individual polypeptide that comprises the mature antibody, targeting them for export from the cell in which they are produced. The signal peptide is cleaved from each heavy chain (Hc) and light chain (Lc) polypeptide after translocation to the ER and prior to secretion. This process is generally highly efficient, producing a high proportion of correctly cleaved Hc and Lc polypeptides. However, mis-cleavage of the signal peptide can occur, resulting in truncation or elongation at the N-terminus of the Hc or Lc. This is undesirable for antibody manufacturing as it can impact efficacy and can result in product heterogeneity. Here, we describe a truncated variant of the Lc that was detected during a routine developability assessment of the recombinant human IgG1 MEDI8490 in Chinese hamster ovary cells. We found that the truncation of the Lc was caused due to the use of the murine Hc signal peptide together with a lambda Lc containing an SYE amino acid motif at the N-terminus. This truncation was not caused by mis-processing of the mRNA encoding the Lc and was not dependent on expression platform (transient or stable), the scale of the fed-batch culture or clonal lineage. We further show that using alternative signal peptides or engineering the Lc SYE N-terminal motif prevented the truncation and that this strategy will improve Lc homogeneity of other SYE lambda Lc-containing mAbs. Biotechnol. Bioeng. 2017;114: 1970-1977. © 2017 Wiley Periodicals, Inc.

Effects of ethyl oleate and microwave blanching on drying kinetics of bitter gourd.

In the present study effects of pre-treatments such as blanching with hot water and microwave, ethyl oleate dipping, and combinations of these treatments on drying characteristics of the bitter gourd (Momordica charantia L.) at various temperature were studied. The overall drying time was reduced significantly in the ethyl oleate treated and microwave blanched samples. The minimum diffusivity (2.65 × 10-8 m2/s) was observed in control samples whereas the maximum diffusivity (3.86 × 10-8 m2/s) was observed in ethyl oleate treated and microwave blanched samples at 50 °C. Ethyl oleate treated and microwave blanched samples dried at lowest temperature (50 °C) showed the lowermost shrinkage ratio (46.04%). The rehydration ratio increased from 3.49 to 4.90 as the temperature increased from 50 to 70 °C for control samples. Combined pre-treatment of ethyl oleate and microwave blanching had resulted in most acceptable drying characteristics and quality of bitter gourd. Drying of the samples were mathematically modelled. The drying characteristics of bitter gourd could be explained suitably by Page drying model.

A systems perspective on brown adipogenesis and metabolic activation.

Brown adipocytes regulate energy expenditure via mitochondrial uncoupling. This makes these fat cells attractive therapeutic targets to tackle the burgeoning issue of obesity, which itself is coupled to insulin resistance, type 2 diabetes, cardiovascular and fatty liver disease. Recent research has revealed a complex network underlying brown fat cell differentiation and thermogenic activation, involving secreted factors, signal transduction, metabolic pathways and gene regulatory components. Given that brown fat is now reported to be present in adult humans, it is desirable to harness the knowledge from each network module to design effective therapeutic strategies. In this review, we will present a systems perspective on brown adipogenesis and the subsequent metabolic activation of brown adipocytes by integrating signaling, metabolic and gene regulatory modules with a specific focus on known 'druggable' targets within each module.

Evaluation of Anterolateral Plating of Distal Third Tibial Fractures.

Background Distal one-third tibial fractures with or without articular involvement can be difficult to manage. Variety of treatment methods have been suggested for these injuries, including conservative treatment, external fixation with or without limited internal fixation, intramedullary nailing, plate fixation (medial or anterolateral) and more recently minimally invasive plate osteosynthesis (MIPO). All of these techniques have advantages and disadvantages. None of these techniques can be considered the "gold standard" for these injuries. Objective The objective of this prospective study was to evaluate the results of anterolateral plating of these fractures. Method Forty-five fractures of distal third of tibia were treated with open reduction and internal fixation with anterolateral tibial plate from December 2011 to December 2016. All the patients were followed up at least for nine months for the study. Radiological union was finally assessed in nine months. Result All the fractures united within nine months of plating without angulation in sagittal or coronal plane. One patient (2%) had limb length shortening of more than one cm. Full range of motion of ankle and knee joint was achieved compared to the normal side by nine months follow up. 17 (38%) patients developed marginal skin necrosis. Three (7%) patients developed superficial wound infection. These complications were seen more in patients in whom posterior below knee slab was used for pre-operative splintage (as compared to calcaneal traction). Conclusion Hence distal one-third tibial fractures with or without articular involvement can be treated with anterolateral tibial plate.

Effect of Sildenafil Citrate on Pulmonary Arterial Systolic Pressure and Sub-maximal Exercise Capacity in Chronic Obstructive Pulmonary Disease.

Background Pulmonary hypertension (PH) often complicates Chronic Obstructive Pulmonary Disease (COPD). Sildenafil reduces pulmonary arterial pressure associated with multitude of diseases. Objective To evaluate the use of Sildenafil in Pulmonary Hypertension associated with COPD. Method This randomized control study enrolled 72 patients: 61 completed the study. Thirtypatients with COPD received Sildenafil 25 mg thrice daily and 31 patients with COPD received optimal medical therapy for four weeks. Symptom assessment and dyspnoea grading was done with modified Borg scale and Modified Medical Research Council (MMRC) grade. The functional assessment was done with WHO functional classification. The estimation of pulmonary arterial systolic pressure and six minute walking distance was done before and after four weeks of the administration of therapy in both groups. Adverse reaction profiling was done for Sildenafil. The primary outcomes were the changes in pulmonary arterial systolic pressure and six minute walk test. The secondary outcomes were change in modified Borg scale for dyspnoea, MMRC grading and WHO functional class. Result The mean decrease in pulmonary arterial systolic pressure in Sildenafil group was significant as compared to controls (9.87+7.84 mmHg Vs 5.93+7.44 mmHg, P=0.048). The mean increase in six minute walk distance was significantly more in cases as compared to controls (48.13+25.79 m Vs 32.59+32.96 m,P=0.047). The changes in modified Borg scale was not significant (1.20+1.92 to 1.55+1.23; P=0.401). There was significant changes in MMRC grade (p=0.037). There was no significant change in WHO functional class after four weeks (p=0.071). Conclusion Sildenafil marginally decreased pulmonary arterial systolic pressure and increased six minute walk distance in COPD patients. It improved MMRC grading without affecting modified Borg's Scale and WHO functional class.

CDK4 in lung, and head and neck cancers in old age: evaluation as a biomarker.

BACKGROUND: Cyclin dependent kinases (CDK) are key factors in promoting the initiation and development of tumors. These kinases are important for maintenance of mitochondrial biogenesis and imbalance in their expression in old age may lead to the oxidative stress. Lung cancer (LC), and head and neck squamous cell carcinoma (HNSCC) are two very prominent cancers in older Indians. Both the cancers are showing increasing trend in older population. The present study assessed serum concentration of one of the kinases; CDK4 in older LC and HNSCC patients. METHODS: The study included 100 subjects each of LC and HNSCC; and older subjects without cancer or any major health problems as controls. Serum CDK4 concentration was estimated using real-time label-free Surface plasmon resonance (SPR) and was verified by western blot. RESULTS: Significant elevation in serum CDK4 was observed in cases with LC and HNSCC compared to controls. HNSCC patients with higher CDK4 expression had distinctly shorter survival than patients with comparatively lower CDK4 expression. No such difference was observed in LC patients. The germ line mutation study of this gene in Exon-2 was performed and none was observed among cases and controls. CONCLUSION: It can be concluded that older patients with HNSCC and lung cancer have raised serums CDK4 levels, which has the potential to emerge as a biomarker in clinical practice.

A Case Report of Post Rabipur (Purified Chick Embryo Rabies Vaccine) Acute Disseminated Encephalomyelitis.

Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease that typically occurs following a viral infection or vaccination. The incidence of ADEM following vaccination has become very low since introduction of non-neural rabies vaccine and only few cases had been reported due to pure chick embryo derived rabies vaccine (PCERV). Here we are reporting a rare case of delayed post vaccinal ADEM.

Does Tranexamic Acid Reduce Perioperative Bleeding in Short Segment Pedicle Screw Fixation in Thoracolumbar Spine Fractures?

INTRODUCTION: Blood loss with spinal surgery is common potential cause of morbidity and often requires blood transfusion. Tranexamic acid (TXA), is effective in reducing bleeding in patients undergoing knee arthroplasty. TXA used in spine surgery studies have included different cases leading to inconsistence of surgical procedures. Purpose of this prospective observational study was to examine effect of TXA decreasing bleeding in short segment pedicle screw fixation for thoracolumbar fractures. METHODS: 38 patients' undergoing short segment pedicle screw for thoracolumbar fractures were enrolled in study from July 2011 to August 2013. There were 28 male and 10 female patients, with an average age of 36.5 years. Patients received 10 mg/kg of TXA or a control 30 minutes intravenously before skin incision and 3 hours post-operative and oral medication for three days. Intraoperative bleeding was estimated by weighing surgical sponges, blood collected by suction container and by subtracting all irrigation fluid. Postoperative bleeding was measured from volume in vacuum drainage bag. RESULTS: Twenty (20) patients were in control group and eighteen(18) to TXA group. There were no statistical differences between groups in terms of age, gender, co-morbidities, and operating time, preoperative Hemoglobin, PT and INR. Intra-operative bleeding in TXA group was significant than in control group. Post-operative drainage and Hemoglobin in first 48 h was reduced compared with placebo in TXA group. Need for post-operative transfusion was nil in TXA group. CONCLUSIONS: Administration of TXA before surgery significantly reduces perioperative bleeding in patients undergoing short segment pedicle screw fixation for thoracolumbar spine fractures.

Herbal remedies for mandibular fracture healing.

PURPOSE: When a bone is fractured it is usually necessary to employ a mechanical means to reduce and maintain the fragments in position. However, healing of the fracture is governed by biological principles, with which the mechanical measures must be coordinated to the end, such that a satisfactory bony union and restoration of form and function are obtained. We have studied the effect of Cissus quadrangularis (Harjor) and Ocimum sanctum (Tulsi), in the healing of mandibular fractures. MATERIALS AND METHODS: A total of 29 cases having a fracture in the body of the mandible were included in the study and divided into three groups. Groups A and B were treated with Ocimum sanctum and Cissus quadrangularis, respectively, and fracture healing was assessed with biochemical markers and the bite force. Group C was the control group. RESULTS: The period of immobilization was the lowest in the Group A followed by Group B. A significant increase in alkaline phosphatase and serum calcium was seen in Group B. The tensile strength in terms of the biting force was the maximum in cases of Group B. CONCLUSION: We conclude that Cissus quadrangularis and Ocimum sanctum help in fracture healing, and use of such traditional drugs will be a breakthrough in the management and early mobilization of facial fractures.

Effect of rifampin on the pharmacokinetics, safety and tolerability of navitoclax (ABT-263), a dual inhibitor of Bcl-2 and Bcl-XL , in patients with cancer.

WHAT IS KNOWN AND OBJECTIVE: Navitoclax, a first-in-class small molecule Bcl-2 family inhibitor, is metabolized in vitro by the hepatic microsomal cytochrome P450 (CYP) enzymes CYP3A4. Drugs that affect CYP3A4 may therefore have an impact on the pharmacological profile of navitoclax. This study evaluated the effects of co-administration of a potent CYP3A4 inducer rifampin on the pharmacokinetic and safety profiles of navitoclax. METHODS: This open-label, fixed-sequence, 2-period study was performed in twelve subjects with non-haematologic or haematologic malignancy that was relapsed or refractory to standard therapy. A 7-day washout period separated the two treatment periods. On Study Day 1 and Day 8, subjects received a single 250 mg oral dose of navitoclax. Rifampin 600 mg was administrated once daily (QD) on Study Day 4 through Day 10. Blood samples for navitoclax assay were collected prior to dosing (0 h) and at a series of time points through 72 h after dosing on Study Day 1 and Day 8. RESULTS AND DISCUSSION: Co-administration of a single 250 mg dose of navitoclax with 600 mg QD doses of rifampin had a negligible effect on the maximum plasma concentration (Cmax ) of navitoclax [ratio of geometric least square means: 0·84 (90% CI: 0·61-1·16)] but moderately decreased the area under the plasma concentration-time curve (AUC) of navitoclax [ratio of geometric least square means: 0·59 (90% CI: 0·44-0·80)]. Rifampin did not affect the half-life of navitoclax. Co-administration of rifampin did not appear to significantly change the safety profile of navitoclax in the limited number of patients evaluated in this study. WHAT IS NEW AND CONCLUSION: Co-administration navitoclax with rifampin moderately decreased navitoclax AUC, which could be partly due to the induction effect of rifampin on CYP3A4. Further assessment on the mechanism of drug interaction is warranted.

An epidemiological study on pattern and incidence of mandibular fractures.

Mandible is the second most common facial fracture. There has been a significant increase in the number of cases in recent years with the advent of fast moving automobiles. Mandibular fractures constitute a substantial proportion of maxillofacial trauma cases in Lucknow. This study was undertaken to study mandibular fractures clinicoradiologically with an aim to calculate incidence and study pattern and the commonest site of fractures in population in and around Lucknow. Patient presenting with history of trauma at various centers of maxillofacial surgery in and around Lucknow were included in this study. Detailed case history was recorded followed by thorough clinical examination, and radiological interpretation was done for establishing the diagnosis and the data obtained was analyzed statistically. Out of 66 patients with mandibular fractures, highest percentage was found in 21-30 years of age with male predominance. Road traffic accidents were the most common cause of fracture with parasymphysis being commonest site. Commonest combination was parasymphysis with subcondyle. There was no gender bias in etiology with number of fracture sites. The incidence and causes of mandibular fracture reflect trauma patterns within the community and can provide a guide to the design of programs geared toward prevention and treatment.

Efficacy of plain radiographs, CT scan, MRI and ultra sonography in temporomandibular joint disorders.

The complexity of structure and functions of the Temporomandibular Joint (TMJ) make the diagnosis of its diseases/disorders difficult. Remarkable progress made in the field of imaging of this joint led us to compare four imaging modalities viz. plain radiographs, CT scan, MRI and ultrasound. We found that MRI was most specific and sensitive for interpretation of soft tissue and inflammatory conditions in the joint, whereas CT examination produced excellent image for osseous morphology and pathology. Plain X-rays are useful for destructive bony changes and sonography is a good in aid in diagnosing disc derangement and is very economical.

Pattern of fungal isolates in cases of corneal ulcer in the western periphery of Nepal.

PURPOSE: To find out the epidemiologic features in 686 consecutive cases of fungal keratitis presenting in a tertiary eye hospital in the western region of Nepal. MATERIALS AND METHODS: A prospective hospital - based study was carried out on 1880 consecutive patients presenting with corneal ulcer in the outpatient department and cornea clinic of Lumbini Eye Institute, Bhairawa, Nepal. The socio-demographic data, predisposing risk factors, prior treatment modalities, laboratory results and the distribution pattern of fungus species were analyzed. RESULTS: Diagnosis of fungus keratitis was established in 686 (36 %) out of the total study group of 1880 cases. The spectrum of fungi isolated were Fusarium species (Fusarium spp.) in 219 (31.9 %), followed by unidentified dematiaceous 151 (22 %), curvularia 122 (17.7 %) and unidentified hyaline in 111 cases (16.1 %). Men (59.3 %) were more commonly affected than women (40.6 %). The young adults age group of 31-40 years was most commonly involved (26.6 %). Corneal trauma (58 %) and topical steroids (12 %) were the most common predisposing risk factors noted. CONCLUSION: In contrast to the other studies done in Nepal, we found Fusarium to be the most common fungal isolate causing corneal ulcer followed by unidentified dematiaceous, unidentified hyaline and curvularia. Corneal trauma was the commonest predisposing risk factor in causing fungal keratitis.