Quantification of vitamin C in the rat brain in vivo using short echo-time 1H MRS.

Both ultrashort echo-time STEAM and MEGA-PRESS-edited spectroscopy were used to validate noninvasive quantification of vitamin C (ascorbate) in the developing rat brain, where changes in ascorbate concentration have been reported. Despite strong overlap with resonances from glutamine, glutamate, glutathione, and macromolecules, reliable quantification of ascorbate (Cramer-Rao lower bounds<0.2 micromol/g) by LCModel analysis of STEAM (TE=2 ms) spectra was possible at 9.4 T. Ascorbate concentrations quantified from the STEAM spectra were in very good agreement with concentrations calculated from fully resolved ascorbate resonances in MEGA-PRESS-edited spectra measured from identical volumes of interest. Ascorbate concentrations measured using STEAM decreased with increasing postnatal rat age, in agreement with published brain ascorbate concentrations measured in vitro using high-performance liquid chromatography (HPLC).     

Granulocytic sarcoma: An atypical presentation in the oral cavity

Acute myelogenous leukemia (AMU is a hematologic disorder that is characterized by an abnormal proliferation of immature myeloid cells. Granulocytic sarcomas are clusters of leukemic myeloid cells that may develop as a result of AML. Oral manifestations of AML are common and often involve enlargements of the gingiva and/or mucosal tissue from direct leukemia cell infiltration. We describe the case history of a 50-year-old man who had an ulcera-tive lesion of the oral mucosa that was determined to be a granulocytic sarcoma of AML-M0 subtype. The combination of both the subtype and clinical presentation of the leukemia makes this presentation unusual, and to the best of our knowledge, of a type that has not been previously reported in the literature.     

Anopheles culicifacies: siblings species composition and its relationship to malaria incidence

Entomological and epidemiological surveys in May, August and November 1985 and March 1986 were conducted in villages in Bulandshahr, a western district in Uttar Pradesh and in three eastern districts, Jaunpur, Ballia and Saran. In Bulandshahr, Anopheles culicifacies sibling species A and B were found, with a predominance of species A. Both Plasmodium vivax and P. falciparum were present and the malaria incidence remained high (SPR, 6-50%) indicating an active transmission. In contrast, in three eastern districts predominance of species B with an occasional occurrence of species A was observed. Malaria cases were almost absent in Ballia and Saran and in Jaunpur 10.3% slide positivity rate was observed in May but in later surveys cases were considerably lower (SPR, 0.5-2.9%) indicating the absence of indigenous transmission. In the eastern districts, malaria parasites are regularly brought in from endemic areas by the migrant labor population. Although An. culicifacies s.l. occurs in both the areas, the difference in malaria incidence appears to be due to the difference in the composition of the sibling species which is, the predominant presence of species A in the western district and its absence in eastern districts. This indicates that species A is responsible for active malaria transmission while species B is not.     

Computed tomography of midline cysts of the prostate

Midline cysts in the male pelvis are a confusing entity due to their relatively infrequent presentation and the uncertainty as to their origin and classification. We report on CT appearance of four cases of midline prostatic cysts. Ultrasound correlation was available in one case. Two patients presented with lower urinary tract symptoms (hematospermia and/or hematuria), and two were asymptomatic, with one case detected on physical examination and one found incidentally on CT. Computed tomography demonstrated a characteristic sharply marginated, low density, homogeneous midline cyst within the prostate. On ultrasound a well defined midline anechoic cystic mass was seen. These cases are illustrated and a discussion of cystic masses in the male pelvis is included.     

Legumain expression in relation to clinicopathologic and biological variables in colorectal cancer.

PURPOSE: Legumain, a novel asparaginyl endopeptidase, has been observed to be highly expressed in several types of tumors including colorectal cancer. However, there is no study examining the relationship of legumain expression to clinocopathologic and biological variables in colorectal cancers. EXPERIMENTAL DESIGN: We investigated legumain expression in 164 primary colorectal cancers, 34 corresponding distant normal mucosa samples, 89 adjacent normal mucosa samples, and 33 lymph node metastases using immunohistochemistry. We also did Western blotting analysis on three additional colorectal cancers and three colonic cell lines. RESULTS: Legumain expression was increased in primary tumors compared with distant or adjacent normal mucosa (P < 0.05), but there was no significant change between primary tumors and metastases (P > 0.05). Legumain expression was positively related to poorer differentiation/mucinous carcinoma (P = 0.04), higher degree of necrosis (P = 0.03) and apoptosis (P < 0.0001), positive proliferating cell nuclear antigen (P < 0.0001) and p53 expression (P = 0.049), and had a positive tendency towards stromelysin 3 (P = 0.058) and PINCH positivity (P = 0.05). The patients with tumors that showed both weak and lower percentage of the legumain expression, either in tumor (P = 0.01) or in stroma (P = 0.04), had a better prognosis. CONCLUSIONS: The legumain expression may be involved in colorectal cancer development and have a prognostic value in the patients.     

Does Squatting Worsen Lower Limb Ischemia in Patients with Peripheral Arterial Disease?

Peripheral arterial disease (PAD) is an important cause of morbidity and mortality in the world affecting up to 20% in people over 70?years of age. The prevalence is increasing in India due to combined effects of increased life expectancy, increased tobacco smoking and increased prevalence of diabetes mellitus. The aim of the study was to examine the hypothesis whether squatting posture reduces blood flow to lower limbs resulting in worsening of symptoms of lower limb ischemia in patients with PAD. 10 patients with arterial disorders due to thromboangiitis obliterans (TAO), atherosclerosis and diabetic macro vascular disease were selected for patients and were compared with 10 healthy volunteers as controls. Clinical examination and duplex scan of posterior tibial artery (PTA) and dorsalis pedis artery (DPA) performed in standing and squatting position in a clinical environment. They were asked about symptoms of numbness, ischemic pain and the results were noted. Results were tabulated and analysed using Microsoft Excel?. Members in the control group complained of numbness of both the limbs after a period of 30?min on an average. In the patients group, members while squatting complained of numbness in the involved limb within 5?min. They complained of ischemic pain in the involved limb within 10?min and developed numbness in the opposite limb in within 15?min. Posterior tibial artery and dorsalis pedis artery pulsations disappeared for the entire duration of squatting in both groups as confirmed by duplex scanning. It may be recommended that patients with established peripheral vascular disease should avoid squatting position, even if it is for a very short period of time. It is desirable to advice such patients to use appropriate structures as supports which will allow them to work without squatting. This may also necessitate a change in occupation.     

Neonatal hyperglycemia alters the neurochemical profile,dendritic arborization and gene expression in the developing rat hippocampus

Hyperglycemia (blood glucose concentration >150 mg/dL) is common in extremely low gestational age newborns (ELGANs; birth at <28 week gestation). Hyperglycemia increases the risk of brain injury in the neonatal period. The long‐term effects are not well understood. In adult rats, hyperglycemia alters hippocampal energy metabolism. The effects of hyperglycemia on the developing hippocampus were studied in rat pups. In Experiment 1, recurrent hyperglycemia of graded severity (moderate hyperglycemia (moderate‐HG), mean blood glucose 214.6 ± 11.6 mg/dL; severe hyperglycemia (severe‐HG), 338.9 ± 21.7 mg/dL; control, 137.7 ± 2.6 mg/dL) was induced from postnatal day (P) 3 to P12. On P30, the hippocampal neurochemical profile was determined using in vivo ¹H MR spectroscopy. Dendritic arborization in the hippocampal CA1 region was determined using microtubule‐associated protein (MAP)‐2 immunohistochemistry. In Experiment 2, continuous hyperglycemia (mean blood glucose 275.3 ± 25.8 mg/dL; control, 142.3 ± 2.6 mg/dL) was induced from P2 to P6 by injecting streptozotocin (STZ) on P2. The mRNA expression of glycogen synthase 1 (Gys1), lactate dehydrogenase (Ldh), glucose transporters 1 (Glut1) and 3 (Glut3) and monocarboxylate transporters 1 (Mct1), 2 (Mct2) and 4 (Mct4) in the hippocampus was determined on P6. In Experiment 1, MRS demonstrated lower lactate concentration and glutamate/glutamine (Glu/Gln) ratio in the severe‐HG group, compared with the control group (p < 0.05). Phosphocreatine/creatine ratio was higher in both hyperglycemia groups (p < 0.05). MAP‐2 histochemistry demonstrated longer apical segment length, indicating abnormal synaptic efficacy in both hyperglycemia groups (p < 0.05). Experiment 2 showed lower Glut1, Gys1 and Mct4 expression and higher Mct1 expression in the hyperglycemia group, relative to the control group (p < 0.05). These results suggest that hyperglycemia alters substrate transport, lactate homeostasis, dendritogenesis and Glu‐Gln cycling in the developing hippocampus. Abnormal neurochemical profile and dendritic structure due to hyperglycemia may partially explain the long‐term hippocampus‐mediated cognitive deficits in human ELGANs.     

Toll-like receptors: Significance,ligands, signaling pathways,and functions in mammals

This review attempts to cover the implication of the toll-like receptors (TLRs) in controlling immune functions with emphasis on their significance, function, regulation and expression patterns. The tripartite TLRs are type I integral transmembrane receptors that are involved in recognition and conveying of pathogens to the immune system. These paralogs are located on cell surfaces or within endosomes. The TLRs are found to be functionally involved in the recognition of self and non-self-antigens, maturation of DCs and initiation of antigen-specific adaptive immune responses as they bridge the innate and adaptive immunity. Interestingly, they also have a significant role in immunotherapy and vaccination. Signals generated by TLRs are transduced through NFκB signaling and MAP kinases pathway to recruit pro-inflammatory cytokines and co-stimulatory molecules, which promote inflammatory responses. The excess production of these cytokines leads to grave systemic disorders like tumor growth and autoimmune disorders. Hence, regulation of the TLR signaling pathway is necessary to keep the host system safe. Many molecules like LPS, SOCS1, IRAK1, NFκB, and TRAF3 are involved in modulating the TLR pathways to induce appropriate response. Though quantification of these TLRs helps in correlating the magnitude of immune response exhibited by the animal, there are several internal, external, genetic and animal factors that affect their expression patterns. So it can be concluded that any identification based on those expression profiles may lead to improper diagnosis during certain conditions.