Tetralogy of Fallot with subaortic membrane: A rare association

Tetralogy of Fallot is the most common cyanotic disease sharing a common anatomic basis but with varied presentation.There are very few described cases of TOF with left sided obstructive lesions. We describe a left ventricular outflow tract obstruction in a 3 year old child in association with TOF. Also we review the available literature for the association of left ventricular obstructive lesions in association with the same.     

Smad4 overexpression causes germ cell ablation and leydig cell hyperplasia in transgenic mice

Members of the transforming growth factor-beta (TGF-beta) superfamily play a variety of important roles in testicular development and function. The tumor suppressor gene, Smad4, is a common mediator of TGF-beta, activin, and bone morphogenetic protein-mediated signaling pathways. To investigate the role of the Smad4 gene during testicular development and function, transgenic mice were generated using a Flag-tagged Smad4 gene driven by 180-bp fragment of the Mullerian inhibiting substance upstream promoter sequence. Three Smad4 transgenic founders (A, B, and G) were detected by Southern blot analysis; line B showed the highest expression of the Smad4 transgene and was further studied. The fertility in F1 generation (B) and F2 generation (BB) of the Smad4 transgenic mice was not impaired. However, in the F3 generation (B2x) all animals were impacted by the overexpression of the Smad4 transgene and two kinds of phenotypes were observed. In one group animals were completely infertile, while in the other group animals were fertile and sired the normal number of pups/litter. These groups are designated as infertile and fertile in the text. Histological evaluation of the testes from the infertile group showed variable degrees of Leydig cell hyperplasia, apoptosis of germ cells, spermatogenic arrest, seminiferous tubule degeneration, and infertility. In the fertile group, there was no apparent change in the histology of the testis except for a slight increase in the number of Leydig cells. Serum follicle-stimulating hormone levels in the adult animals of both groups of Smad4 transgenic male mice were not significantly different from normal littermates; however, testosterone levels in both groups were significantly (P < 0.05) increased. These results suggest that overexpression of Smad4 leads to testicular abnormalities and infertility supporting the hypothesis that the TGF-beta signaling pathways are carefully orchestrated during testicular development. In the absence of normal levels of Smad4 testicular function is compromised.     

Characterization of an extracellular alkaline lipase from Pseudomonas mendocina M‐37

A strain of Pseudomonas mendocina producing extracellular lipase was isolated from soil. The bacterium accumulates lipase in culture fluid when grown aerobically at 30 °C for 24 h in a medium composed of olive oil (1%) as substrate. Pseudomonas mendocina lipase was optimally active at pH 9.0, temperature of 50 °C and was found to be stable between pH 7.0–11.0. The lipase was inhibited by detergents such as SDS and Tween‐80. The enzyme was stable in various organic solvents tested with maximum stability in chloroform followed by toluene and exhibited 1–3 regiospecificity for hydrolytic reaction. This lipase was capable of hydrolyzing a variety of lipidic substrates and is mainly active towards synthetic triglycerides and fatty acid esters that possess a butyryl group. Metal ions like Mg²⁺, Ca²⁺ and Na⁺ stimulated lipase activity, whereas, Cu²⁺, Mn²⁺ and Hg²⁺ ions caused inhibition. (© 2010 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

Multipronged evaluation of genotoxicity in Indian petrol-pump workers

Petrol (gasoline) contains a number of toxicants. This study used human biomonitoring to evaluate the genotoxic effects of exposure to benzene in petrol fumes in 100 Indian petrol-pump workers (PPWs) and an equal number of controls. The study was corroborated with in silico assessments of the Comet assay results from the human biomonitoring study. An in vitro study in human lymphocytes was also conducted to understand the genotoxicity of benzene and its metabolites. In a subset of the population studied, higher blood benzene levels were detected in the PPWs (n = 39; P < 0.01) than the controls (n = 18), and 100-250 ppb benzene was also detected in air samples from the petrol pumps. PPWs had higher levels of DNA damage than the controls (P < 0.01). In addition, the micronucleus assay was performed on lymphocytes from a subset of the subjects, and the micronucleus frequency for PPWs was significantly higher (n = 39; 14.79 +/- 3.92 per thousand) than the controls (n = 18; 7.54 +/- 3.00 per thousand). Human lymphocytes were treated in vitro with benzene and several of its metabolites and assayed for DNA damage with the Comet assay. Benzene and its metabolites produced significant (P < 0.05) levels of DNA damage at and above concentrations of 10 microM. The metabolite, p-benzoquinone, produced the greatest amount of DNA damage, followed by hydroquinone > benzene > catechol > 1,2,4,-benzenetriol > muconic acid. This study demonstrates that, using sensitive techniques, it is possible to detect human health risks at an early stage when intervention is possible. possible.     

Rapidly Progressive Congenital Rhabdomyosarcoma Presenting with Multiple Cutaneous Lesions: An Uncommon Diagnosis and a Therapeutic Challenge

Congenital rhabdomyosarcomas (RMSs) are rare tumors with variable clinical presentations. A 2 month-old, term male neonate (37 weeks, 4 days), weighing 3.2 kg, born to a 24 year-old primigravida, by simple vaginal delivery presented with multiple erythematous papulonodular lesions over his trunk that progressed to his whole body, on the first day of delivery. Prior to conception, his mother was treated for polycystic ovarian disease. On the tenth day, his chest computed tomogram scans revealed multiple, heterogeneously enhancing, bilateral pleural-based soft tissue density nodular lesions, along with multiple soft tissue density lesions, involving skeletal muscles of all his body parts. Microsections from two biopsies (on 10th day and after 2 months) revealed a malignant round cell tumor with cells arranged in a diffuse, solid pattern, comprising embryonal and solid alveolar components. Immunohistochemically, the tumor cells were diffusely positive for desmin, myoD1 and myogenin. Diagnosis of embryonal and alveolar (mixed type) RMS was offered. Further molecular cytogenetic analysis was negative for PAX3-FKHR and PAX7-FKHR. The patient was induced on chemotherapy as per intergroup rhabdomyosarcoma study IV protocol. There was treatment response with near total remission after 8 weeks of treatment. Thereafter, new lesions started appearing that also disappeared after modification of the chemotherapy drugs. However, after 16 months, the baby died of brain metastasis. The present case forms the fourth case report of an aggressive form of a congenital RMS with extensive cutaneous involvement and brain metastasis. A review of previously diagnosed cases of congenital RMSs is discussed herewith.     

A clinical perspective on mucoadhesive buccal drug delivery systems

Mucoadhesion can be defined as a state in which two components, of which one is of biological origin, are held together for extended periods of time by the help of interfacial forces. Among the various transmucosal routes, buccal mucosa has excellent accessibility and relatively immobile mucosa, hence suitable for administration of retentive dosage form. The objective of this paper is to review the works done so far in the field of mucoadhe- sire buccal drug delivery systems （MBDDS）, with a clinical perspective. Starting with a brief introduction of the mucoadhesive drug delivery systems, oral mucosa, and the theories of mucoadhesion, this article then proceeds to cover the works done so far in the field of MBDDS, categorizing them on the basis of ailments they are meant to cure. Additionally, we focus on the various patents, recent advancements, and challenges as well as the future prospects for mucoadhesive buccal drug delivery systems.     

Improvement of Psoriasis During Sunitinib Therapy for Renal Cell Carcinoma

Sunitinib is an oral tyrosine kinase inhibitor, which is indicated for the treatment of renal cell carcinoma and gastrointestinal stromal tumors. The authors report the case of a patient who underwent treatment for renal cell carcinoma and noted additional benefit by improvement in his psoriatic skin lesions. This may be attributed to the antiangiogenic activity of sunitinib by inhibition of vascular endothelial growth factor receptors.