A novel pre-TCRα (pTα) reporter mouse reveals that expression of pTα is confined to the T lineage and does not occur on prethymic progenitors.
Expression of the pre–T cell receptor α (pTα) gene has been exploited in previous studies as a molecular marker to identify tiny cell populations in bone marrow (BM) and blood that were suggested to contain physiologically relevant thymus settling progenitors (TSPs). But to what extent these cells genuinely contribute to thymopoiesis has remained obscure. We have generated a novel pTαiCre knockin mouse line and performed lineage-tracing experiments to precisely quantitate the contribution of pTα-expressing progenitors to distinct differentiation pathways and to the genealogy of mature hematopoietic cells under physiological in vivo conditions. Using these mice in combination with fluorescent reporter strains, we observe highly consistent labeling patterns that identify pTα expression as a faithful molecular marker of T lineage commitment. Specifically, the fate of pTα-expressing progenitors was found to include all αβ and most γδ T cells but, in contrast to previous assumptions, to exclude B, NK, and thymic dendritic cells. Although we could detect small numbers of T cell progenitors with a history of pTα expression in BM and blood, our data clearly exclude these populations as physiologically important precursors of thymopoiesis and indicate that they instead belong to a pathway of T cell maturation previously defined as extrathymic.
Premature closure is a type of cognitive error in which the physician fails to consider reasonable alternatives after an initial diagnosis is made. It is a common cause of delayed diagnosis and misdiagnosis borne out of a faulty clinical decision-making process. The authors present a case of aortic dissection in which premature closure was avoided by the aggressive pursuit of the appropriate differential diagnosis, and discuss the importance of disciplined clinical decision-making in the setting of chest pain.
Purpose. The study was aimed to investigate the frequency of diabetes mellitus type 2 in patients infected with chronic hepatitis C virus and its association with cirrhosis. Patients and Methods. This prospective case series was conducted at Section of Gastroenterology and Hepatology, Isra University Hospital, Hyderabad, over a period of 4 months from June 2009 to October 2009. Hepatitis C virus seropositive patients who were older than 18 years, diabetic or nondiabetic, were included. Basic demographic data collected by questionnaire and laboratory investigations including fasting blood glucose levels, serum cholesterol, and liver function tests were done. A logistic regression model was used to explore the association between diabetic and nondiabetic HCV seropositives and type 2 diabetes mellitus with cirrhosis. Results. A total of 361 patients with hepatitis C were analyzed; the prevalence of type 2 diabetes mellitus in HCV patients was 31.5%. Out of the total number of the participants, 58.4% (n = 211) were cirrhotics, while 41.6% (n = 150) were noncirrhotic HCV seropositives. In multivariate analysis, cirrhotic patients appeared significantly more likely (P = 0.01) to be diabetic as compared with noncirrhotic patients (OR = 2.005, 95% CI: 1.15, 3.43). Conclusion. Advancing age, increased weight, and HCV genotype 3 are independent predictors of type 2 diabetes in HCV seropositive patients, and there is a statistically significant association of cirrhosis observed with type 2 diabetes mellitus.
Acquired facial defects caused by extirpation of neoplasms, congenital malformations or traumatic injury results in a huge functional, cosmetic and psychological handicap in those patients. These defects can be restored by facial prosthesis using different materials and retention methods to achieve a lifelike appearance and function. This clinical report describes a treatment schedule using silicone nasal prosthesis, which is mechanically retained for a patient who has undergone a partial rhinectomy due to basal cell carcinoma of the nose. The prosthesis was made to restore the esthetic appearance of patient with a mechanically retained design using a spectacle glass frame without any prosthetic adhesives so that the patient is more comfortable and confident to resume daily activities.
Mechanical retention; partial rhinectomy; silicone nasal prosthesis; xeroderma pigmentosum
To evaluate the trend of clinical trials in India over the last 4 years compared to the well-established countries using clinical trial registries since the advent of clinical trial registry of India (CTRI).
Materials and Methods:
The data of clinical trials registered in India, United States (US), and European Union (EU) were obtained from websites of CTRI, clinicaltrial.gov and EU clinical trial registry, respectively from July 20, 2007 to August 29, 2011 for a period of 4 years. Trials registered in Australia, Canada, China, and Japan were obtained from WHO's international clinical trial registry platform for the same period. We used search words for the common diseases such as diabetes, hypertension, etc.,
The total number of clinical trials registered during the study period was 67,448 across seven study nations. Clinical trials from India constituted only 2.7% of the total number of trials carried out, compared to US constituting 47% of the total number of trials registered, followed by 18% from EU and 11% from Japan. However, India, China, and Japan have been found to show an increase of 3.7%, 5.1%, and 13.1% increase in the number of trials registered in 2011 compared to 2007. In contrast, US and EU showed a decline of 11.3% and 11.95% respectively in the total number of trials registered in 2011 compared to 2007.
Although India shows gradual increase in trials registered since the advent of CTRI, still it continues to lag behind established countries in clinical research.
Clinical trial registry of India; global clinical trials; world health organization's international clinical trial registry platform
Female urethral injury following pelvic fracture is a rare entity. Due to the absence of large series, management guidelines are still not standardized. Patients can have associated urethrovaginal or vesicovaginal fistula, management of which poses a major challenge to the reconstructive urologist. Spontaneous closure of fistula produced by gynecological or obstetrical injuries have been described in the literature. Spontaneous closure of fistula caused due to pelvic fracture has not been described in the literature.
Mitrofanoff procedure; pelvic fracture; spontaneous closure; urethrovaginal fistula; vesicovaginal fistula
Cells disseminated from primary epithelial tumors into peripheral blood, called circulating tumor cells (CTCs), can be monitored to assess metastases and to provide a surrogate marker of treatment response. Here, we demonstrate how the flexible micro spring array (FMSA) device—a novel microfluidic device that enriches CTCs by two physical parameters: size and deformability—could be used in the rational development of treatment intervention and as a method to study the fundamental biology of CTCs. Cancer cells of different origins were spiked into healthy samples of donor blood to mimic blood samples of metastatic cancer patients. This spiked human blood was filtered using the FMSA device, and the recovered cells were successfully expanded in vitro and in a novel in vivo system. A series of experiments were performed to characterize these cells and to investigate the effect of chemotherapy on the resulting cultures. As few as 20 colon cancer cells in 7.5 mL blood could be isolated with the FMSA device, expanded both in vitro and in vivo and used at 25 cells per well to obtain significant and reliable chemosensitivity data. We also show that isolating a low number of viable patient CTCs and maintaining them in culture for a few weeks is possible. The isolation of viable cancer cells from human blood using the FMSA device provides a novel and realistic means for studying the biology of viable CTCs and for testing drug efficacy on these rare cells—a hypothesis that can be tested in future clinical trials.
circulating tumor cells; drug sensitivity testing; personalized medicine; viable cell capture; microfluidic
Mucosal homeostasis is dependent upon the establishment and maintenance of the cell-cell contacts that comprise the physiological barrier. Breaks in the barrier are linked to multiple diseases such as the inflammatory bowel diseases. While increased cAMP levels limit inflammation by decreasing leukocyte infiltration, the effects of elevated cAMP on intestinal epithelial repair are unknown.
Restitution in animals administered rolipram was monitored by microscopic examination after laser wounding of the intestinal epithelium or in mice treated with dextran sodium sulfate (DSS). In vitro analysis was conducted using IEC6 and T84 cells to determine the role for elevated cAMP in altering Rho-dependent cellular migration signaling pathways.
We show that treatment with rolipram, forskolin, and cAMP-analogs decrease intestinal epithelial cell migration in vitro. In vivo cell imaging revealed that increased cAMP resulted in a decreased cellular migration rate, with cells at the edge displaying the highest activity. As expected, elevated cAMP elicited increased protein kinase A (PKA) activity, in turn resulting in the inactivation and sequestration of RhoA and decreased actin reorganization. The ablation of restitution by cAMP was not restricted to cell culture as forskolin and rolipram treatment significantly decreased epithelial microwound closure induced by the two photon confocal injury model.
Together, these data suggest that administration of cAMP elevating agents paradoxically decrease infiltration of damage-causing leukocytes while also preventing epithelial repair and barrier maintenance. We propose that treatment with cAMP elevating agents severely limits mucosal re-epithelialization and should be contraindicated for use in chronic inflammatory bowel disorders.
cAMP; PKA; restitution; intestinal epithelium; phosphodiesterase inhibitors
There is enormous interest to target cancer stem cells (CSCs) for clinical treatment because these cells are highly tumorigenic and resistant to chemotherapy. Oct4 is expressed by CSC-like cells in different types of cancer. However, function of Oct4 in tumor cells is unclear. In this study, we showed that expression of Oct4 gene or transmembrane delivery of Oct4 protein promoted dedifferentiation of melanoma cells to CSC-like cells. The dedifferentiated melanoma cells showed significantly decreased expression of melanocytic markers and acquired the ability to form tumor spheroids. They showed markedly increased resistance to chemotherapeutic agents and hypoxic injury. In the subcutaneous xenograft and tail vein injection assays, these cells had significantly increased tumorigenic capacity. The dedifferentiated melanoma cells acquired features associated with CSCs such as multipotent differentiation capacity and expression of melanoma CSC markers such as ABCB5 and CD271. Mechanistically, Oct4 induced dedifferentiation was associated with increased expression of endogenous Oct4, Nanog and Klf4, and global gene expression changes that enriched for transcription factors. RNAi mediated knockdown of Oct4 in dedifferentiated cells led to diminished CSC phenotypes. Oct4 expression in melanoma was regulated by hypoxia and its expression was detected in a subpopulation of melanoma cells in clinical samples. Our data indicate that Oct4 is a positive regulator of tumor dedifferentiation. The results suggest that CSC phenotype is dynamic and may be acquired through dedifferentiation. Oct4 mediated tumor cell dedifferentiation may play an important role during tumor progression.
Oct4; Cancer stem cell; Melanoma; Dedifferentiation; hypoxia
We describe a case of a 40-year-old male patient who was found to have multiple myeloma with spontaneous tumour lysis syndrome (TLS), following a compression fracture of the L–2 vertebrae. Multiple myeloma was confirmed by bone marrow analysis and the M–band on serum protein electrophoresis. Hyperuricaemia (26.2 mg/dL), hyperkalaemia (> 7.0 mEq/L), hyperphosphatemia (16.2 mg of phosphorus/dL), normocalcemia and acute kidney injury, prior to anticancer treatment suggested spontaneous TLS. Inciting events for tumour lysis, such as chemotherapy, dehydration and exposure to steroids were absent. Patient received hydration, hypourecemic drugs and haemodialysis. This case report highlights the rare presentation of multiple myeloma with spontaneous TLS.
Hyperphosphatemia; hyperkalaemia; hyperuricaemia; normocalcaemia; renal failure
Dual plate fixation in comminuted bicondylar tibial plateau fractures remains controversial. Open reduction and internal fixation, specifically through compromised soft tissues, has historically been associated with major wound complications. Alternate methods of treatment have been described, each with its own merits and demerits. We performed a retrospective study to evaluate the functional outcome of lateral and medial plate fixation of Schatzker type V and VI fractures through an anterolateral approach, and a medial minimally invasive approach or a posteromedial approach.
Materials and Methods:
We treated 46 tibial plateau fractures Schatzker type V and VI with lateral and medial plates through an anterolateral approach and a medial minimal invasive approach over an 8 years period. Six patients were lost to followup. Radiographs in two planes were taken in all cases. Immediate postoperative radiographs were assessed for quality of reduction and fixation. The functional outcome was evaluated according to the Oxford Knee Score criteria on followup.
Forty patients (33 men and 7 women) who completed the followup were included in the study. There were 20 Schatzker type V fractures and 20 Schatzker type VI fractures. The mean duration of followup was 4 years (range 1-8 years). All patients had a satisfactory articular reduction defined as ≤2 mm step-off or gap as assessed on followup. All patients had a good coronal and sagittal plane alignment, and articular width as assessed on supine X-rays of the knee in the anteroposterior (AP) and lateral views. The functional outcome, as assessed by the Oxford Knee Score, was excellent in 30 patients and good in 10 patients. All patients returned to their pre-injury level of activity and employment. There were no instances of deep infection.
Dual plate fixation of severe bicondylar tibial plateau fractures is an excellent treatment option as it provides rigid fixation and allows early knee mobilization. Careful soft tissue handling and employing minimal invasive techniques minimizes soft tissue complications.
Dual plating; minimal invasive; bicondylar; tibial plateau
Norcantharidin (NCTD) has been reported to induce tumor cell apoptosis. However, the underlying mechanism behinds its antitumor effect remains elusive. We have previously shown that TR3 expression is significantly decreased in metastatic melanomas and involved in melanoma cell apoptosis. In this study, we showed that NCTD inhibited melanoma cell proliferation and induced apoptosis in a dose related manner. NCTD induced translocation of TR3 from nucleus to mitochondria where it co-localized with Bcl-2 in melanoma cells. NCTD also increased cytochome c release from mitochondria to the cytoplasm. These changes were accompanied by increased expression of Bax and cleaved caspase-3 along with decreased expression of Bcl2 and NF-κB2. The effects of NCTD were inhibited by knockdown of TR3 expression using TR3 specific shRNA in melanoma cells. Furthermore, NCTD significantly decreased tumor volume and improved survival of Tyr::CreER; BRAFCa/+; Ptenlox/lox transgenic mice. Our data indicates that NCTD inhibits melanoma growth by inducing tumor cell apoptosis via activation of a TR3 dependent pathway. These results suggest that NCTD is a potential therapeutic agent for melanoma.
norcantharidin; apoptosis; TR3; melanoma
Erythropoietin (Epo) is widely used clinically to treat anemia associated with various clinical conditions including cancer. Data from several clinical trials suggest significant adverse effect of Epo treatment on cancer patient survival. However, controversy exists whether erythropoietin receptor (EpoR) is functional in cancer cells. In this study, we demonstrated that EpoR mRNA expression was detectable in 90.1% of 65 melanoma cell lines, and increased copy number of the Epo and EpoR loci occurred in 30% and 24.6% of 130 primary melanomas, respectively. EpoR knockdown in melanoma cells resulted in diminished ERK phosphorylation in response to Epo stimulation, decreased cell proliferation, and increased response to the inhibitory effect of hypoxia and cisplatin in vitro. EpoR knockdown significantly decreased melanoma xenograft size and tumor invasion in vivo. On the contrary, constitutive activation of EpoR activated cell proliferation pathways in melanoma cells and resulted in increased cell proliferation and resistance to hypoxia and cisplatin treatment in vitro. EpoR activation resulted in significantly larger xenografts with increased tumor invasion of surrounding tissue in vivo. Daily administration of recombinant Epo fails to stimulate melanoma growth in vivo, but the treatment increased vascular size in the xenografts. Increased local recurrence after excision of the primary tumors was observed after Epo treatment. Epo induced angiogenesis in Matrigel plug assays, and neutralization of Epo secreted by melanoma cells results in decreased angiogenesis. These data support that EpoR is functional in melanoma and EpoR activation may promote melanoma progression, and suggest that Epo may stimulate angiogenesis and increase survival of melanoma cells under hypoxic condition in vivo.
Erythropoietin; Erythropoietin receptor; melanoma; hypoxia
Fingerlings of estuarine fishes, Tilapia mossambica and Lates calcarifer were exposed to sub-lethal concentration of mercury and chromium (2.8 ppm) for a period of 28 days. When these fish were exposed to metals concentration, severe gills alterations were observed. But the alteration was less in fish T. mossambica when compared to that of L. calcarife. The fish L. calcarifer exposed to mercury plus chromium, showed lifting up of the epithelium, swelling, hyperplasia, hypertrophy, proliferation of chloride cells, but in mercury treatment, lamellar fusions, fused secondary lamella and necrosis were observed, whereas in T. mossambica the gills disintegration of epithelial cells, desquamated epithelium, hemorrhaged and exhibited complete damage of epithelial cells of lamellae. The Na+, K+-ATPase activity of both gills and plasma showed significant reduction throughout the experiment period in both fishes. The enzyme activity was more drastic in the case of plasma. The results are discussed in relation to the significance of the above enzyme as non-specific biomarkers against environmental stress.
Hg and Cr; histopathology; K+-ATPase; Na+; T. mossambica; L. calcarife
HelpAge India has been facilitating community-managed palliative care program in the villages of Tamil Nadu, India.
To evaluate the effect of perceived quality of life in the elderly in the project villages in rural Tamil Nadu.
Materials and Methods:
It was a community-based evaluation study. Considering the mean difference of 0.6, design effect-2, precision-5%, power 80%, and 10% non-response, a sample size of 450 elderly persons (more than 60 years) was adequate. Sample was selected by two-stage cluster sampling. Tamil version of “WHO-Quality of Life-brief questionnaire” was used. Trained interviewers made house-to-house visits and obtained information by personally interviewing the subjects.
The mean score for perceived physical quality of life in the project area was (10.47 ± 1.80 SD) high than the mean score (10.17 ± 1.82 SD) in the control area (P = 0.013) and the mean score for psychological support (10.13 ± 2.25 SD) in project area was high than the mean score (9.8 ± 2.29 SD) in control area (P = 0.043). There was no effect on domain of social relationship and environment.
In the project villages, the perceived physical quality of life and psychological support among elderly persons was significantly better than the control villages.
Environment; India; Old age; Psychological; Physical; Quality of life; Rural; Social
Aim of the study
This study was made to investigate the antidiabetic, antioxidant and hypolipidemic potential of Cinnamomum tamala, (Buch.-Ham.) Nees & Eberm (Tejpat) oil (CTO) in streptozotocin (STZ) induced diabetes in rats along with evaluation of chemical constituents.
Materials and methods
The GC-MS (Gas chromatography–mass spectrometry) analysis of the oil showed 31 constituents of which cinnamaldehyde was found the major component (44.898%). CTO and cinnamaldehyde was orally administered to diabetic rats to study its effect in both acute and chronic antihyperglycemic models. The body weight, oral glucose tolerance test and biochemical parameters viz. glucose level, insulin level, liver glycogen content, glycosylated hemoglobin, total plasma cholesterol, triglyceride and antioxidant parameters were estimated for all treated groups and compared against diabetic control group.
CTO (100 mg/kg and 200 mg/kg), cinnamaldehyde (20 mg/kg) and glibenclamide (0.6 mg/kg) in respective groups of diabetic animals administered for 28 days reduced the blood glucose level in streptozotocin induced diabetic rats. There was significant increase in body weight, liver glycogen content, plasma insulin level and decrease in the blood glucose, glycosylated hemoglobin and total plasma cholesterol in test groups as compared to control group. The results of CTO and cinnamaldehyde were found comparable with standard drug glibenclamide. In vitro antioxidant studies on CTO using various models showed significant antioxidant activity. In vivo antioxidant studies on STZ induced diabetic rats revealed decreased malondialdehyde (MDA) and increased reduced glutathione (GSH).
Thus the investigation results that CTO has significant antidiabetic, antioxidant and hypolipidemic activity.
Cinnamomum tamala; Cinnamaldehyde; Glibenclamide; Hyperglycaemia; Streptozotocin
This study was undergone to evaluate the in-vivo anti-hyperglycemic and antioxidant potential of ethanolic extract of leaves of Tecomella undulata Seem. on streptozotocin-nicotinamide induced type 2 diabetic rats. Type 2 diabetes was induced by single intraperitoneal injection (i.p.) of 60 mg/kg streptozotocin, 15 minutes after the i.p administration of 110 mg/kg body weight of nicotinamide. The extract has shown significant blood glucose lowering effect in the oral glucose tolerance test (OGTT). The blood glucose level, cholesterol, glycogen contents, glycosylated hemoglobin, and antioxidant parameters (Malondialdehyde and Glutathione level) were estimated from the blood plasma by using standard kits to demonstrate the hypoglycemic and antioxidant effect in treated animals. The data showed that the extract have significant influence on the above biochemical parameters. Thus ethanolic fraction of the plant Tecomella undulata can be used as new candidate for antihyperglycemic and antioxidant.
Tecomella undulata; Streptozotocin; Diabetic rats; Malondialdehyde; Glycosylated hemoglobin
Diabetes may alter renal glucose reabsorption by sodium (Na+)-dependent glucose transporters (SGLTs). Radiolabeled substrates are commonly used for in vitro measurements of SGLT activity in kidney cells. We optimized a method to measure glucose uptake using a fluorescent substrate, 2-(N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino)-2-deoxyglucose (2-NBDG).
Uptake buffers for 2-NBDG were the same as for 14C-labeled α-methyl-d-glucopyranoside ([14C]AMG). Cell lysis buffer was optimized for fluorescence of 2-NBDG and Hoechst DNA stain. Uptake was performed on cultures of primary mouse kidney cells (PMKCs), the LLC-PK1 proximal tubule cell line, or COS-7 cells transiently overexpressing mouse SGLT1 or SGLT2 by incubating cells at 37°C in buffer containing 50–200 μM 2-NBDG. Microscopy was performed to visualize uptake in intact cells, while a fluorescence microplate reader was used to measure intracellular concentration of 2-NBDG ([2-NBDG]i) in cell homogenates.
Fluorescent cells were observed in cultures of PMKCs and LLC-PK1 cells exposed to 2-NBDG in the presence or absence of Na+. In LLC-PK1 cells, 2-NBDG transport in the presence of Na+ had a maximum rate of 0.05 nmol/min/μg of DNA. In these cells, Na+-independent uptake of 2-NBDG was blocked with the GLUT inhibitor, cytochalasin B. The Na+-dependent uptake of 2-NBDG decreased in response to co-exposure to the SGLT substrate, AMG, and it could be blocked with the SGLT inhibitor, phlorizin. Immunocytochemistry showed overexpression of SGLT1 and SGLT2 in COS-7 cells, in which, in the presence of Na+, [2-NBDG]i was fivefold higher than in controls.
Glucose transport in cultured kidney cells can be measured with the fluorescence method described in this study.
Bulimia nervosa (BN) is a type of feeding disorder that starts in adolescence and presents a variety of symptoms, recurrent vomiting in the oral cavity that may reach down to the larynx – similarly to gastro-esophageal reflux, causing laryngeal and voice disorder alterations.
These studies aimed at surveying the literature and investigate the studies that considered BN a risk factor for voice disorders and its epidemiology, complications, diagnostic criteria, and management.
Materials and Methods:
A review of the literature was done based on a survey of BIOMED CENTRAL and COCHRANE @ OVID databases, which are linked to the IMU ezproxy virtual library (http://ezp.imu.edu.my/menu). The keywords “bulimia nervosa”, “teenage complications” and “voice changes” were used. Citations with summaries were chosen to limit the topic, for the period between 2000 and 2010, in English.
Of the ninety three papers we found, twenty three were used as a basis for this review. Among them, only three discuss BN as an etiology factor associated with voice changes in adult women, and we did not find any paper associating this with bulimic teenagers.
It is necessary to observe laryngeal and vocal signs and symptoms associated with BN, especially in teenagers whose voices are going through a period of change. The contribution of this type of investigation, which should begin with a clinical history, is essential for minimizing the complications of bulimia nervosa. Thus, adolescents and adults with voice disorders should be investigated in greater detail.
Bulimia nervosa; teenage complications; voice changes
Epidermal melanocytes play an important role in protecting skin from ultraviolet (UV) rays, and are implicated in a variety of skin diseases. Here, we developed an efficient method for differentiating induced pluripotent stem cells (iPSCs) into melanocytes. We first generated iPSCs from adult mouse tail-tip fibroblasts (TTFs) using retroviral vectors or virus-free piggyBac transposon vectors carrying murine Sox2, Oct3/4, cMyc and Klf4. The TTF-derived iPSC clones exhibited similar morphology and growth properties as mouse embryonic stem (ES) cells. The iPSCs expressed ES cell markers, displayed characteristic epigenetic changes and formed teratomas with all three germ layers. The iPSCs were used to generate embryoid bodies (EBs) and were then successfully differentiated into melanocytes by treatment with growth factors. The iPSC-derived melanocytes expressed characteristic melanocyte markers and produced melanin pigment. Electron microscopy showed that the melanocytes contained mature melanosomes. We manipulated the conditions used to differentiate iPSCs to melanocytes and discovered that Wnt3a is not required for mouse melanocyte differentiation. This report shows that melanocytes can be readily generated from iPSCs, providing a powerful resource for the in vitro study of melanocyte developmental biology and diseases. By inducing iPSCs without viruses, the possibility of integration mutagenesis is alleviated, providing iPSCs are more compatible for cell replacement therapies.
iPSCs; melanocytes; reprogramming; differentiation
Doxorubicin-induced cardiomyopathy in cancer patients is well established. The proposed mechanism of cardiac damage includes generation of reactive oxygen species, mitochondrial dysfunction and cardiomyocyte apoptosis. Exposure of adult rat cardiomyocytes to low levels of DOX for 48 h induced apoptosis. Analysis of protein expression showed a differential regulation of several key proteins including the voltage dependent anion selective channel protein 2 and methylmalonate semialdehyde dehydrogenase. In comparison, proteomic evaluation of DOX-treated rat heart showed a slightly different set of protein changes that suggests nuclear accumulation of DOX. Using a new solubilization technique, changes in low abundant protein profiles were monitored. Altered protein expression, modification and function related to oxidative stress response may play an important role in DOX cardiotoxicity.
Doxorubicin; cardiomyopathy; proteomics
Rubinstein-Taybi syndrome (RSTS) is a rare congenital neurodevelopmental disorder, characterized by postnatal growth deficiency, typical dysmorphic features, broad thumbs and toes, and mental retardation. Very few cases are reported in literature from developing countries. Diagnosis is often delayed due to non-familiarity with the characteristic features of this syndrome.
To report 11 cases of RSTS and to review the current literature.
SETTINGS AND DESIGN:
Retrospective study conducted in genetic and metabolic unit of a tertiary care teaching hospital in north India over a period of 3½ years.
MATERIALS AND METHODS:
11 patients with diagnosis of RSTS were identified, and their case sheets were reviewed.
Developmental delay was presenting complaint in 10 patients, and seizure in 1 case. 7 patients had microcephaly (head circumference below −3 SD), and a prominent beaked nose was seen in 9 patients. The intelligence quotient (IQ) varied from 22-62 in 7 patients who had mental retardation. The most notable features in hands were broadness, shortening, and flattening of the distal phalanx of thumbs or great toes. Additionally, we also noted webbing of neck, microphthalmia, and pachygyria (on MRI brain) in 1 patient each.
The diagnosis of RSTS is primarily clinical and based on characteristic phenotype that is often combined with a variety of somatic anomalies. An early diagnosis facilitates appropriate genetic counseling and in planning the management.
Beaked nose; broad thumbs; broad toes; dysmorphism; mental retardation
Diabetes mellitus is a potentially morbid condition with high prevalence worldwide thus being a major medical concern. Experimental induction of diabetes mellitus in animal models is essential for the advancement of our knowledge and understanding of the various aspects of its pathogenesis and ultimately finding new therapies and cure. Experimental diabetes mellitus is generally induced in laboratory animals by several methods that include: chemical, surgical and genetic (immunological) manipulations. Most of the experiments in diabetes are carried out in rodents, although some studies are still performed in larger animals. The present review highlights the various methods of inducing diabetes in experimental animals in order to test the newer drugs for their anti-diabetic potential.
Streptozotocin; alloxan; diabetic rats; animal models; diabetes