Effects of propranolol in combination with radiation on apoptosis and survival of gastric cancer cells in vitro

The microRNA-17-92 (miRNA-17-92) cluster, at chromosome 13q31-q32, also known as oncomir-1, consists of seven miRNAs that are transcribed as a polycistronic unit. Over-expression of miRNA-17-92 has been observed in lymphomas and other solid tumors. Whether miRNA-17-92 expression affects the response of tumor cells to radiotherapy is not addressed so far. In the present study, we studied the effects of miRNA-17-92 on the radiosensitivity of human mantle cell lymphoma (MCL) cells Z138c. Over-expression of miRNA-17-92 significantly increased survival cell number, cell proliferation and decreased cell death of human MCL cells after different doses of radiation. Immunoblot analysis showed that phosphatase and tension homolog (PTEN) and PHLPP2 was down-modulated and pAkt activity was enhanced in MCL cells after over-expressing miRNA-17-92 after irradiation. These findings are the first direct evidence that over-expression of miRNA-17-92 cluster significantly increases the radioresistance of human MCL cells, which offers a novel target molecule for improving the radiotherapy of MCL in clinic.     

Salmonella meningitis: report of five cases

Five cases of salmonella meningitis were encountered during a period of 5 years at Medical College Hospital, Rohtak. All were male children and four of them were below 5 years of age. Salmonella etiology had not been though of prior to laboratory confirmation in any of these cases. Early specific diagnosis followed by appropriate therapy produced good response in all except one infant who expired. Of the 5 salmonella isolates three were S. typhimurium and two S. typhi.     

Radioprotective and antioxidant properties of low-altitude Podophyllum hexandrum (LAPH).

The development of nontoxic yet effective radioprotectors is needed because of the increasing risk of human exposure to ionizing radiation. We have reported that high-altitude Podophyllum hexandrum (HAPH) confers a radioprotective effect in in vitro and in vivo models. The present study reports on the antioxidant and radioprotective properties of low-altitude Podophyllum hexandrum (LAPH), from which the toxic compound podophyllotoxin has been partially removed during the extraction process. Using HPLC,we estimated the relative content of two marker compounds, podophyllotoxin and podophyllotoxin glycoside, in low-altitude Podophyllum extract (LAPE) and found them to be 23.3% and 9.50%, respectively. The ferrous ion chelation potential of LAPE was estimated using the 2,2 bipyridyl assay, and the activity was found to be increased concomitantly with the increase in its concentration, with a maximal inhibition at 25 microg/mL (42.20%) as compared to quercetin (34.9%). The electron donation potential of LAPE was also evaluated, because the antioxidant activities of natural products are known to bear a direct correlation with their ability to donate electrons. The concentration required to attain unit absorbance values at 700 nm were 0.230541+/-0.09 and 0.041+/-0.06 for butylated hydroxyl toluene and LAPE, respectively, indicating a higher antioxidant activity of LAPE. The free radical scavenging ability of LAPE was also assessed and exhibited a dose-dependant increase (1-100 microg/mL), comparable to that of quercetin at 25 microg/mL. The role of LAPE in protecting DNA was evaluated, and it was found that LAPE (30 microg/mL) rendered its maximum radioprotection against the 250 Gy-induced damage in the plasmid (pBR322) relaxation assay. LAPE significantly inhibited radiation-induced, iron/ascorbate- and combined stress (iron/ascorbate and radiation)-induced formation of TBARS (p<0.05). We conclude that LAPH, with its easy accessibility, ease of cultivation, multifarious radioprotective properties, and role as a renewable source of bioactive constituents, along with its low associated toxicity (due to partial removal of podophyllotoxin), enhances its possible use for human clinical applications.     

Pronator Quadratus Hemangioma (PQH): A Rare Case Report and Review

The intramuscular hemangioma is a rare clinical entity in the upper extremity. Pronator quadratus hemangioma poses a considerable morbidity in the functional quality of life of an individual. MRI remains the gold standard modality in diagnosing this rare entity. Additionally, histopathological examination of the lesion corroborates for the same. PQH follows an individualized protocol in the management of the tumour. A 35-year-old female presented with pain over her right wrist from past 1 year which was dull aching, non-radiating, localised to the palmar aspect of distal 1/3rd of the right forearm. There was no history of trauma or infection over the right wrist. Swelling was present over the palmar aspect of distal 1/3rd of right forearm, which was non-pulsatile, non-fluctuant, non-transilluminant, non-compressible, non-reducible and skin over the swelling was pinchable. The movements of the right wrist were painful and restricted. There was no distal neurovascular deficit. The MRI of her right wrist and hand suggested the presence of low flow vascular malformation within pronator quadratus muscle. The patient underwent excision biopsy of pronator quadratus in toto without any neurological complications. No recurrence was noted in the follow-up period for 12 months. The pronator quadratus hemangioma is a rare clinical entity where the natural course of disease and pathophysiology remains controversial. MRI serves as the gold standard in the diagnosis of intramuscular hemangioma. The management of such tumour has to be individualized based on the functional needs of the patient. The natural course of the disease has to be elicited to decrease the morbidity and enhance the functional quality of life of the patient.     

Clofazimine induced nail changes

Two cases of lepromatous leprosy with erythema nodosum leprosum who were on high doses of clofazimine, showed discoloration of nail plate, subungual hyperkeratosis and onycholysis. These nail changes gradually disappeared when the dose of clofazimine was reduced.     

Dialysis membrane-induced oxidative stress: role of heme oxygenase-1

Dialysis membranes have been reported to induce monocyte apoptosis. We studied the role of oxidative stress in the induction of dialysis membrane-induced monocyte apoptosis. Superoxide dismutase, a superoxide scavenger, prevented dialysis membrane-induced monocyte apoptosis. Similarly, other antioxidants also inhibited dialysis membrane- induced apoptosis. In addition, the interaction of dialysis membranes with monocytes was associated with the generation of molecules leading to oxidative stress such as superoxide and TBARS. Interestingly, pre-induction of heme oxygenase (HO)-1 by hemin prevented dialysis membrane-induced monocyte apoptosis, whereas inhibition of HO-1 activity (treatment with tin protoporphyrin, SN-P) enhanced dialysis membrane-induced monocyte apoptosis. We suggest that oxidative injury associated with dialysis membrane and monocyte interaction plays a role in monocyte injury. Pre-induction of HO-1 may attenuate dialysis membrane-induced monocyte apoptosis.     

Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction

Hypertension promotes atherosclerosis and is a major source of morbidity and mortality. We show that mice lacking T and B cells (RAG-1^−/− mice) have blunted hypertension and do not develop abnormalities of vascular function during angiotensin II infusion or desoxycorticosterone acetate (DOCA)–salt. Adoptive transfer of T, but not B, cells restored these abnormalities. Angiotensin II is known to stimulate reactive oxygen species production via the nicotinamide adenosine dinucleotide phosphate (NADPH) oxidase in several cells, including some immune cells. Accordingly, adoptive transfer of T cells lacking the angiotensin type I receptor or a functional NADPH oxidase resulted in blunted angiotensin II–dependent hypertension and decreased aortic superoxide production. Angiotensin II increased T cell markers of activation and tissue homing in wild-type, but not NADPH oxidase–deficient, mice. Angiotensin II markedly increased T cells in the perivascular adipose tissue (periadventitial fat) and, to a lesser extent the adventitia. These cells expressed high levels of CC chemokine receptor 5 and were commonly double negative (CD3⁺CD4⁻CD8⁻). This infiltration was associated with an increase in intercellular adhesion molecule-1 and RANTES in the aorta. Hypertension also increased T lymphocyte production of tumor necrosis factor (TNF) α, and treatment with the TNFα antagonist etanercept prevented the hypertension and increase in vascular superoxide caused by angiotensin II. These studies identify a previously undefined role for T cells in the genesis of hypertension and support a role of inflammation in the basis of this prevalent disease. T cells might represent a novel therapeutic target for the treatment of high blood pressure.     

Factors related to diagnostic persistence of attention deficit/hyperactivity disorder in Turkish children and adolescents

Objective: Attention-deficit/hyperactivity disorder (ADHD) is one of the most frequently occurring mental disorders in children and adolescents. The purpose of this study was to determine diagnostic persistence three years after the first clinical evaluation and to investigate the factors relating to diagnostic persistence in children and adolescents with ADHD. Methods: The study included 183 children and adolescents who were evaluated in the first admission. Of 183 children and adolescents, 142 children and adolescents were evaluated in the second admission and only the data of 142 children and adolescents were analysed in the study. Diagnostic persistence was defined as having met the full criteria for ADHD on second evaluation. Symptom severity of ADHD was determined using the Turgay DSM-IV-based Child and Adolescent Behavior Disorders Screening and Rating Scale-Parents Form (T-DSM-IV-S). Intelligence level was assessed through the Wechsler Intelligence Scale for Children-Revised. Results: Of the children included in the study, 77.5% (n?=?110) were determined to have ADHD diagnostic persistence. Low intelligence levels, younger age and higher T-DSM-IV-S inattention and conduct disorder scores were associated with diagnostic persistence. ADHD diagnosis in children and adolescents tends to continue at high rates. Conclusions: Determination of the risks related to ADHD diagnostic persistence may contribute to improved treatment planning and interventions.