Heat Shock Protein-Mediated Protection Against Cisplatin-Induced Hair Cell Death

Cisplatin is a highly successful and widely used chemotherapy for the treatment of various solid malignancies in both adult and pediatric patients. Side effects of cisplatin treatment include nephrotoxicity and ototoxicity. Cisplatin ototoxicity results from damage to and death of cells in the inner ear, including sensory hair cells. We showed previously that heat shock inhibits cisplatin-induced hair cell death in whole-organ cultures of utricles from adult mice. Since heat shock protein 70 (HSP70) is the most upregulated HSP in response to heat shock, we investigated the role of HSP70 as a potential protectant against cisplatin-induced hair cell death. Our data using utricles from HSP70^−/− mice indicate that HSP70 is necessary for the protective effect of heat shock against cisplatin-induced hair cell death. In addition, constitutive expression of inducible HSP70 offered modest protection against cisplatin-induced hair cell death. We also examined a second heat-inducible protein, heme oxygenase-1 (HO-1, also called HSP32). HO-1 is an enzyme responsible for the catabolism of free heme. We previously showed that induction of HO-1 using cobalt protoporphyrin IX (CoPPIX) inhibits aminoglycoside-induced hair cell death. Here, we show that HO-1 also offers significant protection against cisplatin-induced hair cell death. HO-1 induction occurred primarily in resident macrophages, with no detectable expression in hair cells or supporting cells. Depletion of macrophages from utricles abolished the protective effect of HO-1 induction. Together, our data indicate that HSP induction protects against cisplatin-induced hair cell death, and they suggest that resident macrophages mediate the protective effect of HO-1 induction.     

Traumatic globe luxation: A case report

Globe luxation is a rare clinical event. Most of the cases are usually traumatic, although spontaneous globe luxation has also been reported. The majority of the posttraumatic cases are usually associated with the injury or fracture of the bony orbit. We report here a case of globe luxation that occurred per se without any injury to the orbital or maxillo-facial bony structures.     

Label-free detection of creatinine using nitrogen-passivated fluorescent carbon dots

In the field of biochemistry and biosensing, the passivation of carbon dots using nitrogen dopants has attracted great attention, as this can control their photoluminescence (PL) properties and quantum yield. To date, in the fabrication of a sensing probe, the impact of the chemical composition of the passivating molecule remained unexplored. In this work, we chose a series of different nitrogen-rich precursors (such as urea, thiourea, cysteine, and glycine) and ascorbic acid to synthesize nitrogen-doped carbon dots (NCDs). A significant change in their surface states was obtained due to the evolution of variable contents of amino, pyridinic and pyrrolic nitrogen species, which is evident from X-ray photoelectron spectroscopy, and this leads to an increment in their PL quantum yields (PLQY ∼ 58%) and average lifetime values. Spectroscopic analysis revealed that a rise in the ratio of pyrrolic : amino groups on the surface of carbon dots cause a bathochromic shift and generate excitation-dependent properties of NCDs. Besides, these NCDs were used as fluorescence off–on sensing probes, where a PA-infested NCD solution was used to detect creatinine. Chiefly, fluorescence restoration was achieved due to the formation of Jaffe chromogen between creatinine and PA. However, all nitrogen-passivated carbon dot surfaces do not respond similarly towards creatinine and only non-amino-rich NCDs exhibit the maximum (50%) PL turn-on response. The PL turn-off–on methodology showed a satisfactory good linearity range between 0 and 150 μM with a detection limit of 0.021 nM for creatinine. Three input molecular logic gates were also designed based on the turn-off–on response of the NCDs@PA towards creatinine. Additionally, for analytical method validation, real-sample analysis was performed for creatinine, which showed good recoveries (93–102%) and verified that nitrogen passivation tailored the physicochemical properties and enhanced the sensing ability.

The role of passivation in CDs using different nitrogen precursors to evaluate its sensing proficiency towards creatinine quantification.     

Study of the KIR gene profiles and analysis of the phylogenetic relationships of Rajbanshi population of West Bengal,India

The natural killer (NK) cells have distinct receptors called killer cell immunoglobulin-like receptors (KIR) which are responsible for regulating NK cell responses to infections and malignancy. The extensive variations in the number and type of KIR genes can be used as a tool to understand the differentiation of populations and also for tracing genetic background. In this study, we have aimed to analyze the KIR gene polymorphism in the Rajbanshi population of West Bengal, India. To our knowledge this is the first report on the KIR gene polymorphism in the Rajbanshis, a population widely distributed in the Terai and Dooars region of West Bengal, India. Herein, we have studied the gene distribution of 14 KIR genes (KIR3DL1–3DL3, KIR 2DL1–2DL5, 2DS1–2DS5 and 3DS1) and two pseudogenes (KIR3DP1 and 2DP1). The gene frequencies and genotypic frequencies were calculated, based on which statistical analyses were performed. The presence of a considerable number of genotypic profiles suggests substantial diversity in the KIR gene pool of the Rajbanshis in the region studied. Apart from the framework genes (KIR2DL4, 3DL2, 3DL3 and 3DP1) present in all the individuals, the gene frequencies of other KIR genes varied between 0.84 and 0.15. Moreover the KIR polymorphisms of the Rajbanshis were also compared with that of available published data of the populations of other ethnicities. Though the Rajbanshi population showed a tendency to cluster with other Indian population based on KIR gene frequencies, the influence of Tibeto–Burman Lineage on their KIR genotypic profiles cannot be overlooked. Furthermore, evidences from previously published data on Y chromosome haplogroup diversity study on Rajbanshis support the view. Our results will not only help to understand the genetic background of the Rajbanshi population, but also in tracing the population migration events in the North–Eastern part of India and in illustrating the extensive genetic admixture amongst the different linguistic groups of the country and also in KIR-related disease researches.     

Chitosan and gelatin biopolymer supplemented with mesenchymal stem cells (Velgraft®) enhanced wound healing in goats (Capra hircus): Involvement of VEGF,TGF and CD31

AimCell-based therapy has emerged as promising strategy for chronic and impaired wounds treatment. Current research is focused on developing biomaterial systems that act as a niche for mesenchymal stem cells (MSCs) to promote wound healing through paracrine molecular cascading. This study was aimed to evaluate the wound healing potential of Velgraft, a ready-to-use biodegradable artificial skin substitute, on excision wound in goats.Materials and methodsTwelve male goats were randomized divided in to three groups of four animals each. After infliction of surgical wound, Velgraft and Soframycin were applied on wounds of the animals of Groups II and III while Group I (sham operated) served as control. Wound diameters were measured at pre-defined time-points for determination of progressive wound healing up to 28 days. Skin sections were stained using Hematoxylin and eosin (H&E) for examining the histoarchitectural changes, Masson trichome staining for ascertaining collagen synthesis and immunohistochemistry for expression of CD31, VEGF and TGF-β1 proteins to determine post-treatment angiogenesis in the inflicted wounds.ResultsVelgraft application appreciably enhanced wound closure by day 21 which was confirmed through restoration of the normal skin architecture as evident based on histopathological examination and characterized by complete regeneration of epidermal layers, collagen fibers, blood capillaries and hair follicular formation. Stimulation of angiogenesis markers was also observed at different time-points post-Velgraft application; which is suggestive of the improved angiogenesis and vasculogenesis.ConclusionVelgraft facilitates wound healing by augmenting early wound closure, enhancing collagen synthesis and deposition, trichosis development and promoting revascularization and epidermal layers restoration.     

Withania somnifera ameliorates lead-induced augmentation of adrenergic response in rat portal vein

Objectives:

Present study was undertaken to elucidate the ameliorating potential of Withania somnifera root extract (WRE) against lead-induced augmentation of adrenergic response in rat portal vein.

Materials and Methods:

In-vitro studies were conducted on effect of lead alone and lead+WRE on rat-isolated portal vein while in-vivo studies were done in three groups of 12 rats each; Group-II and III received 0.5% lead acetate and 1.0% WRE + 0.5% lead acetate, respectively, in drinking water for 12 weeks whereas group-I served as control. Adrenaline and noradrenaline levels in brain and blood were determined by HPLC assay while vascular reactivity of portal vein to lead and WRE was determined by measuring the isometric tension.

Results:

Following in-vitro exposure, lead did not alter the contractile effect of phenylephrine. In-vivo studies revealed that contractile effect of lead on portal vein was significantly potentiated and it was antagonized by prazosin (10^-7 M) and WRE (1%). WRE treatment significantly reduced elevated blood noradrenaline (37.80%) and restored noradrenaline level in brain (39.39%) in lead-exposed animals. These values were almost comparable to the control group. But it failed to significantly affect the blood and brain adrenaline levels.

Conclusions:

Results suggest that following pre-exposure of rats to WRE, lead-induced augmentation of alpha₁-adrenoceptors mediated response was reversed possibly by regulating catecholamine release from nerve endings. Thus, WRE may be useful in therapeutic management of lead-induced hypertension.KEY WORDS: Alpha₁-adrenergic response, lead, portal vein, rat, Withania somnifera     

Chronic diarrhea and facial dysmorphism in children--a clue to men 2B syndrome: a case report

Medullary thyroid cancer (MTC) is a highly malignant tumor of the thyroid gland in children, rarely diagnosed and treated by pediatric oncologists. The authors describe a 9-year-old male who presented with facial dysmorphism and history of chronic diarrhea before being diagnosed with advanced MTC. Familiarity with its clinical variants, associated RET protooncogene mutation and its clinical implication, can lead to early identification of this aggressive tumor. To date, surgery remains the only definitive therapy, with continuing dismal prognosis in metastatic disease. However, evolving newer therapeutic strategies like tyrosine kinase inhibitors and pretargeted radioimmunotherapy (pRAIT) may provide hope to children with this aggressive tumor.     

Retrospective and prospective study of singapore swing method on healing of mastoid cavity

Chronic suppurative otitis media with cholesteatoma is a common problem. The majority of ENT surgeons find the canal wall down operation to be the safest and simplest means of treating cholesteatoma. The 'Singapore Swing' is a method of promoting healing of mastoid cavity. In this study our main objective was to do Singapore Swing technique in larger number of cases, have long term follow-up and to compare its results with other mastoid operations in which obliteration has not been used. Patients of cholesteatoma were divided into case group and control group. The case group (26 patients) was operated by canal wall down procedure with Singapore Swing obliteration while the control group (62 patients) was operated by same method without any obliteration. Both retrospective and prospective studies were done. Time period of drying of mastoid cavity, numbers of visits to the hospital and hearing status were observed. Subjective satisfaction score of patient (0-10) and Surgeon's satisfaction score (fully satisfied, partially satisfied and not satisfied at all) were measured in both the groups. The time of drying of cavity was <2?months in 88.5% of cases, while 27.5% of controls. Mean time of drying of cavity was 46?days (1??months) in case group, while it was 89?days (3?months) in control group. Gain in air conduction was 11-30?dB in 33.3% cases and 15.7% of controls. 2 patients in control group had deterioration of 1-10?dB in air conduction. Subjective satisfaction score was 8-10 in 42.4% patients in case group, while 25% in control group. Surgeon was fully satisfied in 73% patients of case group and 45% patients of control group. The study suggested that Singapore Swing technique provides a dry, small and stable cavity with better hearing in less time.     

Novel approach to laparoscopic resection of tumours of the distal pancreas

Background: Laparoscopic resection for small lesions of the pancreas has recently gained popularity. We report our initial experience with a new approach to laparoscopic spleen‐preserving distal pancreatectomy so that the maximum amount of normal pancreas can be preserved while ensuring adequate resection margins and preservation of the spleen and splenic vessels. Methods: Three patients underwent laparoscopic distal pancreatectomy with spleen and splenic vessel preservation over a 2‐month period. Surgical techniques and patient outcomes were examined. Results: All three patients were females, with ages ranging from 31 to 47 years. Two patients underwent resection using the conventional medial‐to‐lateral dissection as the lesion was close to the body or proximal tail of the pancreas. The third patient had a lesion in the distal tail of the pancreas and surgery was carried out in a lateral‐to‐medial manner. This new approach minimized excessive sacrifice of normal pancreatic tissue for such distally located lesions. The splenic artery and vein were preserved in all cases and there was no significant difference in clinical outcome, operative time or intraoperative blood loss. Conclusion: Laparoscopic distal pancreatectomy with preservation of the spleen and splenic vessels is a feasible surgical technique with acceptable outcome. We have shown that a tailored approach to dissection and pancreatic transection based on the location of the lesion allows the maximum amount of normal pancreatic tissue to be preserved without additional morbidity. Although the conventional ‘medial‐to‐lateral’ approach is recommended for more proximal tumours of the pancreas, distal lesions can be safely addressed using the ‘lateral‐to‐medial’ approach.