Oriental theileriosis associated with a new genotype of Theileria orientalis in buffalo (Bubalus bubalis) calves in Uttar Pradesh, India.

Theileria orientalis is known to cause a benign infection in cattle and buffalo (Bubalus bubalis). However, the Ikeda and Chitose genotypes of the parasite cause lethal disease in beef and dairy cattle. Recently an outbreak of clinical oriental theileriosis occurred in buffalo calves in a Government Animal Husbandry and Agricultural Farm located in Uttar Pradesh, India. Examination of Giemsa stained thin blood smears revealed typical rod-shaped T. orientalis piroplasms in the erythrocytes. The clinical signs included pyrexia, nasal discharge, lacrimation, lethargy, inappetence and anaemia with varying degrees of paleness of the visible mucous membranes. Vascular congestion in internal organs, pulmonary emphysema and consolidation of lungs, focal areas of necrosis in the heart with mononuclear cell infiltration, focal mononuclear cell aggregation in the cortex and tubular degeneration of the kidney were significant necropsy findings. The T. orientalis major piroplasm surface protein (MPSP) gene was amplified by polymerase chain reaction (PCR) using specific primers. The nucleotide sequence analysis of the PCR product revealed 84.8% identity between the T. orientalis Uttar Pradesh isolate and other reference genotypes available in the public domain. Furthermore, the phylogenetic analysis of the MPSP gene sequence ratified that this is a new genotype of T. orientalis. This is the first report of a clinical outbreak of oriental theileriosis in Indian buffalo calves caused by a novel genotype of T. orientalis.

Physical interaction of estrogen receptor with MnSOD: implication in mitochondrial O2.- upregulation and mTORC2 potentiation in estrogen-responsive breast cancer cells.

Augmented reactive oxygen species levels consequential to functional alteration of key mitochondrial attributes contribute to carcinogenesis, either directly via oxidative DNA damage infliction or indirectly via activation of oncogenic signaling cascades. We previously reported activation of a key oncogenic signaling cascade via mammalian target of rapamycin (mTOR) signaling complex-2 (mTORC2) owing to estrogen receptor (ER-α)-dependent augmentation of O2.- within the mitochondria of 17-ß-estradiol (E2)-stimulated breast cancer cells. Manganese superoxide dismutase (MnSOD) is the principal mitochondrial attribute governing mitochondrial O2.- homeostasis, raising the possibility that its functional alteration could be instrumental in augmenting mitochondrial O2.- levels in breast cancer cells. Here we show ER-dependent transient inhibition of MnSOD catalytic function in breast cancer cells. Catalytic function of MnSOD is tightly regulated at the post-translational level. Post-translational modifications such as phosphorylation, nitration and acetylation represent key regulatory means governing the catalytic function of MnSOD. Acetylation at lysine-68 (K68) inhibits MnSOD catalytic activity and thus represents an important post-translational regulatory mechanism in human cells. Using reciprocal immunoprecipitation and proximity ligation assay, we demonstrate the occurrence of direct physical interaction between ER-α and MnSOD in human breast cancer cells, which in turn was associated with potentiated acetylation of MnSOD at K68. In addition, we also observed diminished interaction of MnSOD with sirtuin-3, the key mitochondrial deacetylase that deacetylates MnSOD at critical K68 and thereby activates it for scavenging O2.-. Consequently, compromised deacetylation of MnSOD at K68 leading to its inhibition and a resultant buildup of O2.- within the mitochondria culminated in the activation of mTORC2. In agreement with this, human breast cancer tissue specimen exhibited a positive correlation between acetyl-MnSODK68 levels and phospho-Ser2481 mTOR levels. In addition to exposing the crosstalk of ER-α with MnSOD post-translational regulatory mechanisms, these data also unravel a regulatory role of ER/MnSOD interaction as an important control switch for redox regulation of ER-α-responsive oncogenic signaling cascades. Furthermore, our study provides a mechanistic link for ER-α-dependent O2.- potentiation and resultant mTORC2 activation in breast cancer cells.

Pressure ulcer management in paraplegic patients with a novel negative pressure device: a randomised controlled trial.

OBJECTIVE: A randomised controlled trial to compare negative pressure wound therapy (NPWT) using our innovative negative pressure device (NPD) and the standard pressure ulcer (PU) wound dressing of in traumatic paraplegia patients. METHOD: This study was conducted in the Department of Orthopaedic Surgery at King George's Medical University, Lucknow, India. Traumatic paraplegia patients with sacral pressure ulcers of stage 3 and 4 were randomised into two groups, receiving either standard wound dressings or NPWT with NPD. The outcomes monitored were length, width (surface area), depth of PU, exudates, discharge, tissue type (necrotic, slough and red granulating tissue), and cost-effectiveness during 0 to 9 weeks follow-up. RESULTS: Length and width were significantly (p<0.01) decreased in NPWT group as compared with standard care group at week 9. At weeks 1, 2 and 3, depth was significantly (p<0.05) higher in NPWT group, whereas at week 9 a significant reduction (p=0.01) was observed. Exudates were significantly (p=0.001) lower in NPWT group at weeks 4 and 9. Conversion of slough into red granulation tissue was significantly higher in NPWT group (p=0.001). Discharge became significantly (p=0.001) lower in NPWT at week 2 and no discharge was observed after week 6. In all parameters, decrease was larger in NPWT group compared with standard care, which was significant for exudates type (p=0.03) and tissue type (p=0.004). CONCLUSION: Our NPD is better than standard wound care procedures and cost-effective for management of PU.

A study on local expression of NF-κB, CCL2 and their involvement in intratumoral macrophage infiltration in breast cancer.

NF-κB has been implicated in mechanisms promoting inflammation in tumor microenvironment leading to breast cancer metastasis. Owing to critical role of CCL2 during metastasis, particularly in its capacity to act as a chemoattractant for macrophages and their precursors i.e monocytes, we decided to explore if pro-metastatic function of NF-κB could be attributable to CCL2 and/or macrophage infiltration. Through our study we provide experimental and clinical evidence in support of co-ordinated expression of chemokines CCL2, NF-κB and intratumoral macrophage content particularly with respect to breast cancer, with an additional evidence of these three variables being key determinant for poor prognosis and diminished survival amongst breast cancer patients both independently as well in a coordinated manner. The mean fold increase in mRNA expression level of NF-κB and CCL2 indicated that it was over expressed 13.57 and 13.18 fold respectively in tumor tissue as compared to adjacent normal tissue. Among these Immunohistochemistry expression of CD68 marker showed that 62 patients (66.7%) had low/moderate CD68 expression while 31 patients (33.3%) had strong expression. All three variables viz.NF-κB, CCL2 and CD68 showed significant (p<0.05 or p<0.01 or p<0.001) respectively associations with both clinicopathological (except CD68 with stage) and hormone receptors (ER, PR and Her2/neu) and their co-expressions indicating these as predictors of breast cancer. In this study we decipher the possible molecular mechanism by way of which NF-κB may promote breast cancer metastasis. Our study has clinical relevance as it establishes significance of these three variables as potential predictive markers to be employed in breast cancer.

Diet-induced modulation of pharmacokinetics of albendazole in Sahiwal cattle.

The influence of diet type and pre-treatment fasting on the kinetic disposition of albendazole was evaluated in Sahiwal heifers following oral and intra-ruminal administration of the drug. The anthelmintically active moiety albendazole sulphoxide appeared early and was eliminated early in cattle offered green fodder, with decreased maximum concentration (C max) and area under concentration-time curve (AUC) when the drug was administered both through oral and intra-ruminal routes. Further, the elimination half-life (t ½ß) revealed significantly increased values for albendazole sulphoxide in cattle administered albendazole through the intra-ruminal route. An increased AUC and t ½ß is reflective of increased bioavailability of albendazole in animals offered dry fodder. Increased values (P <  0.05) of C max, time to C max (T max), AUC and t ½ß for albendazole sulphoxide occurred in cattle with a pre-treatment 24-h fast, resulting in its increased bioavailability. Extrapolation of data of the active metabolite albendazole sulphoxide levels in terms of drug-parasite contact revealed increased exposure of parasites to the drug in cattle administered albendazole through the intra-ruminal route and with 24-h pre-treatment fasting.

Cyclooxygenase-2 inhibition attenuates hypoxic cancer cells induced m2-polarization of macrophages.

Tumor-associated macrophages (TAMs), represent a major subpopulation of tumor infiltrating immune cells. These alternatively activated M2-polarized macrophages are well known for their pro-tumor functions. Owing to their established role in potentiating tumor-neovasculogenesis and metastasis, TAMs have emerged as promising target for anti-cancer immunotherapy. One of the key TAMs related phenomenon that is amenable to therapeutic intervention is their phenotype switching into alternatively activated M2-polarized macrophages. Hindering macrophage polarization towards a pro-tumor M2 phenotype, or better still reprogramming the M2 like TAMs towards M1 subtype is being considered a beneficial anti-cancer strategy. Hypoxic tumor milieu has been proposed as one of the most plausible factor governing M2-polarization of macrophages. We recently demonstrated that hypoxic tumor cells imparted a pro­angiogenic M2 skewed phenotype to macrophages. Furthermore, sizeable body of data indicates for participation of cyclooxygenase-2 (COX-2) in macrophage polarization. Concordantly, inhibition of COX-2 is associated with impaired macrophage polarization. Prompted by this in the current study we decided to explore if inhibition of COX-2 activity via chemical inhibitors may prevent hypoxic cancer cell induced M2-polarization of macrophages. We observed that treatment with Flunixin meglumine, an established preferential inhibitor of COX-2 activity markedly inhibited hypoxic cancer cell induced of M2-polarization of macrophages thereby indicating for usage of COX-2 inhibition as possible anti-cancer treatment modality.

Intravenous infusion for the treatment of diabetic and ischaemic non-healing pedal ulcers.

Diabetic and ischaemic non-healing pedal ulcers have a tendency for chronicity and increased chances of infection, which may threaten the viability of the foot. Systemic administration of therapeutic agents may be insufficient in these cases. We have assessed the role of retrograde venous perfusion (RVP) for the treatment of nine diabetic and 10 ischaemic non-healing pedal ulcers. Agents used were soda bicarbonate, heparin, lignocaine, gentamicin and pentoxiphylline. Five of nine diabetic non-healing ulcers showed complete healing and the remaining four improved. The complete recovery in the cases of diabetic ulcer occurred in 10-24 days (mean 16 days), while ischaemic ulcers took 10-14 days for complete recovery (mean 13.6 days). There was a reduction of rest pain in all 10 patients with ischaemic disease; five patients showed complete healing of ulcers, and the other five improved significantly. In two patients, pre-gangrene changes were reversed. RVP is a useful adjunct to conservative or surgical treatment of non-healing pedal ulcers. Its main impact was in improving ischaemia and promoting healing.

Tuberculous appendicitis in India.

Tuberculous appendicitis (TBA) is a rare condition. The present study has been conducted to study its prevalence and presentation. This retrospective study was performed in the Department of Surgery, NSCB Government Medical College, Jabalpur, MP, India, in 870 consecutive appendectomies performed between January 1991 and December 2000. Of 870 consecutive appendicular specimens, 10 cases of primary (1.1%) and 16 of secondary TBA (1.8%) were encountered. Results of all pre-operative investigations were non-specific and the diagnosis was made only after histopathology. The prevalence of TBA in this study was 2.9%. Although it is a rare condition, its possibility should be kept in mind by clinicians as well as pathologists. All surgically removed appendix specimens should be histopathologically examined, whether or not the specimens are macroscopically normal. Given antitubercular treatment in addition to appendectomy, patients recover without complications.

Influence of the dwarfing gene dw on egg production and viability under summer heat stress.

1. Dwarf egg layer (Narmada XL) dwarf broiler (DB) and normal bodied sib (NB) hens were studied under cyclic summer hot and dry heat stress of 21.1 to 45.5 degrees C for a period of 50 d. The genotype effect for egg production was significant (P less than 0.01). 2. N-XL and DB genotypes laid 12.1% more eggs than NB. Egg production declined by 3.17, 1.27 and 3.25% for a rise in temperature (maximum) of 1 degree C for N-XL, DB and NB genotypes respectively. 3. Egg production in Narmada XL declined by 42% compared to 25% in the dwarf broilers. The regression coefficients differed significantly. 4. For polygenically identical DB and NB broiler breeder hens the heat stressor significantly reduced egg production 1.98% more in the NB genotype compared with DB with a 1 degree C rise in temperature. 5. Mortality was less in the N-XL as compared to DB, but NB hens showed 11.7% more mortality than dwarfs.