Metabolic remodeling precedes mitochondrial outer membrane permeabilization in human glioma xenograft cells

Glioma cancer cells adapt to changing microenvironment and shift from mitochondrial oxidative phosphorylation to aerobic glycolysis for their metabolic needs irrespective of oxygen availability. In the present study, we show that silencing MMP-9 in combination with uPAR/cathepsin B switch the glycolytic metabolism of glioma cells to oxidative phosphorylation (OXPHOS) and generate reactive oxygen species (ROS) to predispose glioma cells to mitochondrial outer membrane permeabilization. shRNA for MMP-9 and uPAR (pMU) as well as shRNA for MMP-9 and cathepsin B (pMC) activated complexes of mitochondria involved in OXPHOS and inhibited glycolytic hexokinase expression. The decreased interaction of hexokinase 2 with mitochondria in the treated cells indicated the inhibition of glycolysis activation. Overexpression of Akt reversed the pMU- and pMC-mediated OXPHOS to glycolysis switch. The OXPHOS un-coupler oligomycin A altered the expression levels of the Bcl-2 family of proteins; treatment with pMU or pMC reversed this effect and induced mitochondrial outer membrane permeabilization. In addition, our results show changes in mitochondrial pore transition to release cytochrome?c due to changes in the VDAC-Bcl-XL and BAX-BAK interaction with pMU and pMC treatments. Taken together, our results suggest that pMU and pMC treatments switch glioma cells from the glycolytic to the OXPHOS pathway through an inhibitory effect on Akt, ROS induction and an increase of cytosolic cytochrome c accumulation. These results demonstrate the potential of pMU and pMC as therapeutic candidates for the treatment of glioma.     

Dedifferentiated adenoid cystic carcinoma of the lacrimal gland

A rare variant of adenoid cystic carcinoma is the dedifferentiated sarcomatoid form, which has previously been reported in the hard and soft palate, maxillary sinus, submandibular glands, and nasal cavity. The authors report the first case of a dedifferentiated sarcomatoid adenoid cystic carcinoma occurring in the lacrimal gland, that of a 52-year-old man. The patient presented with a 4-month history of diplopia, decreased vision, and right upper eyelid swelling. Radiographic imaging showed a soft tissue mass in the extraconal compartment superolateral to the right eye. The patient subsequently underwent surgical debulking. Histologic examination of the tissue revealed classic cribiform adenoid cystic carcinoma and a sarcomatous component consisting of malignant spindle cells and fusiform cells arranged in whorls. Dedifferentiation is a well-established phenomenon in salivary gland tumors that is associated with aggressive behavior and poor prognosis; however, the exact nature of such dedifferentiated neoplasms remains unclear.     

Sporotrichosis in Uttarakhand (India): a report of nine cases

Background Sporotrichosis is a chronic granulomatous infection caused by Sporothrichum schenckii. The disease has worldwide distribution. Majority of cases from India are reported from North‐eastern states. Methods The demographic, clinico‐investigative profile and therapeutic results of nine patients with cutaneous sporotrichosis attending the Dermatology Outdoor Department between January 2005 and June 2006 have been compiled. Results Out of nine (male‐4, female‐5) patients, five had lymphocutaneous‐type sporotrichosis while four had fixed cutaneous sporotrichosis. The average age of these patients was 40.8 years. The duration of complaints ranged from 1 month to 15 months (average 8.6 months). Two patients were able to recall traumatic injury. Six patients had lesions over lower extremities, two over face and one over upper extremity. Histopathologically, all cases showed granulomatous process with mixed inflammatory infiltrate comprising of lymphocytes, plasma cells, histiocytes and small neutrophil abscesses. Two cases were positive for fungal cells on PAS staining. Fungal culture on skin tissue was positive in all cases. Eight patients were treated with saturated solution of potassium iodide (SSKI) and they responded very well to SSKI in 12–16 weeks. One patient was pregnant and therefore was advised thermotherapy. Conclusion Sporotrichosis is also present in north‐western region of India as it is reported from north‐eastern part. This is the first series of cutaneous sporotrichosis being reported from Uttarakhand, a state situated in the north‐western region of India.     

Peak expiratory flow rate of rural school children from Wardha district,Maharashtra in India

Background  Peak expiratory flow rate (PEFR) recording is an essential measure in the management and evaluation of asthmatic children. The PEFR can be measured by a simple instrument—peak expiratory flow meter. The aim of this study was to determine the normal PEFR in rural school children from Wardha district of Maharashtra state, India. Methods  The PEFR was measured in 1078 healthy rural school children, living in Wardha district, Maharashtra using the Mini-Wright peak flow meter. All measurements were obtained in a standing position and the best out of three trials was recorded. Anthropometric measurements, weight, height, and mid-upper-arm circumference (MAC) were recorded, and body surface area (BSA) and body mass index (BMI) were calculated. Results  Positive correlation was seen between age, height, weight and PEFR. The regression equations for PEFR were determined for boys and girls separately. The boys had higher values than the girls at all heights. The prediction equation for PEFR based on height was PEFR = 3.64 height (cm) − 257.86 (R=0.47, R ²=0.22) for female; PEFR = 4.7 height (cm) − 346.51 (R=0.62, R ²=0.38) for male. Conclusion  PEFR is a reliable measurement, which can be used routinely and regularly in rural areas for assessment of airway obstruction and prediction formula derived for use in this population.     

Clinical progression of chikungunya fever during acute and chronic arthritic stages and the changes in joint morphology as revealed by imaging

This longitudinal follow-up study of 203 patients with serologically confirmed chikungunya (CHIK) virus infection describes the clinical features of CHIK fever during the first and tenth months of illness. During the acute stage CHIK fever presents with a wide array of symptoms. The foremost chronic symptoms at the end of a month were rheumatism (75%) and fatigue (30%). During the tenth month of follow-up the symptoms/signs observed were joint pain/swelling (46%), fatigue (13%) and neuritis (6%). The cure rate at the end of 9 months was 51%. Among the patients who had joint pain, 36% (34/94) met the American College of Rheumatology criteria to classify them as having rheumatoid arthritis. A subpopulation of the patients with joint pain (20/94) was tested for rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibody, and the joints were imaged by X-ray and magnetic resonance imaging (MRI). All tested negative for RF and one tested positive for anti-CCP. A radiolucent lesion in the X-ray was seen in the bones of five patients. The MRI findings were joint effusion, bony erosion, marrow oedema, synovial thickening, tendinitis and tenosynovitis. The study proves with relative certainty that CHIK arthritis is chronic inflammatory erosive arthritis, which has implications for management of the infection.     

Inferior Turbinate osteoma — rare cause of nasal obstruction

Osteomas are common benign tumors of the paranasal sinus, with a predilection for the frontal sinus. We report a rare case of inferior turbinate osteoma in a 54 year old lady. The osteoma was resected completely by endoscopic sinus surgery and the patient was relieved of symptoms.