A long-term nutritional assessment of maxillary cancer patients undergoing prosthodontic rehabilitation after surgery: A longitudinal study.

Purpose: To evaluate the nutritional status (NS) of patients planned for maxillectomy and prosthodontic rehabilitation using three nutritional assessment methods. Methods: This longitudinal study enrolled 18 planned maxillectomy patients following the inclusion and exclusion criteria. NS was evaluated at five stages: before surgery (S0), 2 weeks after surgery (S1), 3 months after insertion of intermediate obturator (S2), just before fabrication of definitive obturator (S3), and 3 months after insertion of definitive obturator (S4) using two nutritional assessment tools i.e. Patient Generated -Subjective Global Assessment (PG-SGA) &Nutritional risk index (NRI); and body composition indicators i.e. body mass index (BMI), fat free mass (FFM), total body water (TBW), skeletal muscle mass (SMM) and skeletal muscle mass index (SMMI).To determine the changes in patient's nutritional status among different time points Repeated Measure ANOVA with Bonferroni post hoc adjustments was used. Results: Out of 18 patients, 12 were completed the study. NS of maxillectomy patients deteriorates significantly (p < .05) till stage S2. At S3, significant improvement occurred as compared to stage S2, but it remained significantly less than pre-surgical level. However, at stage S4, all parameters were statistically comparable to S0 (p > .05) except for PG-SGA (p < .001) and SMM (p = .044). Conclusion: NS of maxillectomy patients worsen post surgically due to surgical morbidity and adverse effects of radiotherapy (RT) but improves with post-surgical healing, resolution of sequel of RT and improved oral function due to well-adapted obturator prosthesis.

A Cross-Sectional Study on Central Sensitization and Autonomic Changes in Fibromyalgia.

Fibromyalgia is a multi-symptomatic disorder characterized by generalized pain. The pathophysiology of fibromyalgia is supposedly an interplay between central nervous system hyper-responsiveness, autonomic dysfunction, and peripheral pain. In this cross-sectional study, the objective was to assess central sensitization and autonomic activity in patients with fibromyalgia compared with control. Fifty adults diagnosed with fibromyalgia by the modified American College of Rheumatology 2010 criteria and an equal number of age- and sex-matched controls participated in the study in an urban tertiary care hospital. Central sensitization was assessed by history and by evidence of increased prefrontal cortical activity as measured by cortical oxygenation using functional near-infrared spectroscopy. Autonomic activity was assessed by heart rate variability, electrodermal activity, and deep breathing test in three physiological states: rest, sympathetic stress (cold pressor test), and deep breathing. Mann-Whitney U-test, paired t-test, Wilcoxon test, and Friedman test with Bonferroni a priori were used to analyze the data. Cortical activity was significantly higher in the fibromyalgia group than control. There was no significant difference in autonomic activity between the fibromyalgia and control groups. In the fibromyalgia group, variable degrees of sympathetic hyperactivity and normal parasympathetic activity were observed. Central sensitization may be playing a primary role in the pathophysiology of generalized pain in fibromyalgia.

Dietary spices in health and diseases: I.

Spices are heterogeneous collections of a wide variety of volatile and non-volatile staple dietary additives. India with its wide climatic conditions and topographical features naturally possesses wide variety of medicinal flora. Spices have a diverse array of natural phytochemicals that have complementary and overlapping actions, including antioxidant effects, modulation of detoxification enzymes, stimulation of immune system, reduction of inflammation, modulation of steroid metabolism and antibacterial and antiviral effects. In the present essay, various studies on effects of different well characterized spices on molecular, cellular, autocrine, paracrine and endocrine mechanisms and their role in neuromodulation, immunoinodulation, anti inflammatory, antioxidant, anti-carcinogenic, antimutagenic and psychoactive phenomena have been reviewed.

Dietary spices in health and diseases (II).

Dietary spices influence various systems in the body such as gastrointestinal, cardiovascular, reproductive and nervous systems resulting in diverse metabolic and physiologic actions. As inheritors of a long tradition of the use of spices in diet as well as in indigenous medicines we know that these are treatments often honed over centuries with well-established reputations for efficacy. A rigorous review of these manifold beneficial effects may provide a fair basis for prescription in many clinical conditions where confirmed modern drug treatments do not exist or as adjunct therapy to reduce the dosage or the, risk of side effects. This essay attempts to adjudicate the traditional use of dietary spices based on factual research evidence for their multivalent actions as health promoting dietary additives as well as putative therapeutic agents.

Upper airway obstruction in patients with goiter studies by flow volume loops and effect of thyroidectomy.

The patient with goiter and his or her physician frequently overlook symptoms of upper respiratory obstruction. Conventional radiology is the accepted method for detecting upper airway obstruction in these patients. Flow volume loops provide additional information on airflow dynamics. Twenty-five patients of goiter undergoing surgery were evaluated for upper airway obstruction by symptomatology, conventional radiology, and flow volume loops. Flow volume loops were repeated 1 month after surgery. Ten (40%) patients had mild symptoms on direct questioning. Tracheal deviation, compression, or both were noted in eight (32%) patients on radiology. Flow volume loops detected upper airway obstruction in 15 (60%) patients. Surgery resulted in normalization of all preoperative abnormal curves. The flow volume loop is a simple noninvasive method for detecting upper airway obstruction in patients with goiter. Abnormal upper airway dynamics are present in more patients with goiter than previously recognized, and relief of this obstruction should be an important aspect of thyroid surgery.

Gastro-intestinal effects of Indian spice mixture (Garam Masala).

Spices are a part of diet all over the world but the variety and quantity consumed in tropical countries is particularly significant. The intestinal transit time of Indians is shorter, and their stool weight larger than that of Europeans on a comparable fibre intake. Ingestion of chilli is associated with a faster whole gut transit time. There is hardly any human work on the effects of spices on intestinal transit or gastric emptying. To explore the effects of spices on gastro intestinal transit this study was conducted on 18 well nourished healthy human adult volunteers using Radiolabelled Idli with or without Garam Masala. On gastric scintigraphy the gastric emptying time was much faster in subjects when spicy meal was given. The t1/2 of the spicy meal, 40.09 +/- (p < 0.05) thus implying a faster transit through the stomach. In 17 out of the 18 subjects t1/2 of the spicy meal was consistently lower than that of spicefree meal. The lag phase of gastric emptying showed no significant difference. There was a tendency towards slower gastrocolic transit with Spicefree meal but more subjects need to be done to confirm this.

Sperm and oocyte treatments to improve the formation of male and female pronuclei and subsequent development following intracytoplasmic sperm injection into bovine oocytes.

This study assessed pronuclear formation, the chromosomal constitution, and the developmental capacity of bovine zygotes formed by intracytoplasmic injection of oocytes with sperm, treated or not with dithiothreitol (DTT). Oocytes were matured in vitro for 22-24 h and then centrifuged so that sperm, prepared by swim-up in the presence or absence of 5 mM DTT, could be injected into the cleared area of the ooplasm. Injected oocytes were activated by treatment with 5 microM ionomycin (5 min) and, after a 3-h interval, with 1.9 mM 6-dimethylaminopurine (DMAP) for 3 h. They were then cocultured with bovine oviductal epithelial cells in M199. Sperm treatment resulted in a significantly higher proportion of male pronucleus formation 16 h after injection (40% vs. 11%; p < 0.0001) and a significantly higher rate of blastocyst development (24% vs. 10%; p < 0.005). Sixty-one percent of blastocysts produced with treated sperm were diploid. Of 12 blastocysts produced with treated sperm and sexed by a polymerase chain reaction, 4 were male and 7 female, and in one a definite diagnosis could not be made. Embryo transfer (2 embryos per heifer) resulted in pregnancies in 6 of 16 recipients at Day 49, but none was carried to term. These results show that the efficiency of bovine intracytoplasmic sperm injection can be improved by sperm pretreatment with DTT and by oocyte activation with ionomycin plus DMAP, although the developmental capacity of the resulting embryos remains limited.

Autonomic dysfunction and peripheral vasodilatory response in diabetes.

Twenty three diabetes mellitus patients were investigated for peripheral vasodilatory response in relation to degree of autonomic dysfunction. The non-insulin dependent diabetes mellitus (NIDDM) patients had significant degree of autonomic dysfunction. Based on standard scoring system for evaluating autonomic dysfunction, diabetics were divided into 'borderline' (n = 12) and 'severe' (n = 11) diabetic autonomic neuropathy (DAN) groups. The severe DAN patients showed significantly lower pressor response when compared to borderline DAN patients. Severe DAN was also associated with significant peripheral vascular dysfunction. The severe DAN patients largely had no clinical manifestation of peripheral vascular dysfunction. Thus, at subclinical level patients with significant autonomic dysfunction do exhibit peripheral vascular dysfunction.

Hepatocyte growth factor induces activation of Nck and phospholipase C-gamma in lung carcinoma cells.

Hepatocyte growth factor (HGF), a mesenchyme derived growth factor, promotes cell growth, cell motility, and morphogenesis in a variety of epithelial cells. The diverse responses are transduced across the cell membrane by the met/HGF receptor, a product of c-met protooncogene. The met/HGF receptor recruits a variety of second messenger molecules which relay the diverse intracellular responses of HGF. In this study, we show that HGF autophosphorylates and activates met/HGF receptor. The activated met/HGF receptor then physically associates with and activates phospholipase C-gamma (PLC-gamma). Furthermore, upon ligand stimulation, tyrosine-autophosphorylated met/HGF receptor also activates Nck oncogene product. Taken together, our results suggest that the receptor activation leads to formation of a complex in which PLC-gamma and Nck oncogene product co-exist with the activated met/HGF receptor, and that the Nck oncogene product is an important component of HGF signaling in Calu-1 and A549 cells.

Vasopressor responses in autosomal dominant cerebellar ataxia.

Thirteen patients with autosomal dominant cerebellar ataxia were investigated for autonomic functions using standard tests. Patients showed no significant reduction in parasympathetic responses as measured by heart rate response to slow breathing and Valsalva manoeuvre. Measurement of blood pressure response to isometric exercise, cold exposure and 70 degrees head-up tilt showed a significant decrease in sympathetic pressor response.

Selective tumorigenesis in non-parenchymal liver epithelial cell lines by hepatocyte growth factor transfection.

Hepatocyte growth factor (HGF) has been recently suggested to contribute to tumorigenesis by an autocrine mechanism in fibroblast cells overexpressing its receptor, the MET/HGFR protein. Since epithelial cells represent the primary physiologic target of HGF, we investigated whether inappropriate expression of HGF by epithelial cells which normally express MET/HGFR may also contribute to tumorigenesis. We have transfected a full length rat HGF gene into three mouse epithelial cell lines, one derived from breast (MM55) and two (BNL CL.2 and NMuLi) representing liver non-parenchymal epithelial cells (NPEC). We confirmed the presence of the transfected gene by Southern blot analysis, the production of HGF protein by immunofluorescence, and the preservation of HGF biologic activity by bio-assay. In comparison to untransfected cells, all three HGF-transfected cell lines displayed high level MET/HGFR autophosphorylation and increased ability to proliferate in media containing low serum. The two HGF-transfected liver NPEC lines, but not the HGF-transfected mammary cell line, displayed loss of cell contact growth-inhibition and acquired a markedly increased ability to form colonies in soft agar. Furthermore, the NPEC HGF-transfected cell lines formed much larger tumors in nude mice than the untransfected counterparts, with extensive invasion and sporadic lung metastases. These results demonstrate that overexpression of HGF in at least some epithelial cells contribute to tumorigenesis, and furthermore suggest a possible role for the HGF-MET/HGFR system in the progression of certain epithelial tumors.

Hepatocyte growth factor-induced signal transduction in two normal mouse epithelial cell lines.

We have investigated HGF-induced signal transduction in two normal mouse epithelial cell lines (M23 and MM55). Both cell lines display HGF-induced mitogenesis and high level HGF-induced autophosphorylation of MET/HGFR. In both M23 and MM55 cells, HGF induces association with MET/HGFR and increased tyrosine phosphorylation of the SH2-domain containing proteins PI3K, GAP and NCK. PLC-gamma exhibited neither HGF-induced increases in tyrosine phosphorylation nor an association with MET/HGFR in these cell lines. Additionally, HGF induced increased transcription of c-fos, c-jun, junB, junD, and c-myc early response genes in both cell lines. We therefore suggest that the second messenger proteins PI3K, GAP and NCK, and possibly the protein products of the c-fos, c-jun, junB, junD and c-myc genes, are important elements in the HGF-induced mitogenic pathway in the normal mouse epithelial cell lines M23 and MM55.

Evidence for autocrine basis of transformation in NIH-3T3 cells transfected with met/HGF receptor gene.

NIH-3T3 cells transformed with met/HGF receptor gene proliferate in the absence of serum and growth factors. Immunocytochemical staining with anti-HGF antibody revealed intense HGF staining in the transfected cells. Additionally, these cells secrete bioactive HGF as evidenced by the ability of the conditioned media to stimulate met/HGF receptor phosphorylation in epithelial cells, and to promote migration of bovine adrenal capillary endothelial cells in a modified Boyden chamber assay. The migration of endothelial cells could be specifically inhibited by anti-HGF antibody but not by an irrelevant antibody. Suramin, a drug known to disrupt ligand-receptor interactions, inhibits the serum and growth-factor free proliferation, and the endogenous phosphorylation of met/HGF receptor in the transformed cells. Taken together, our data suggests an autocrine mode of transformation in NIH-3T3 cells transfected with met/HGF receptor gene.

PDGF-independent activation of PDGF-beta receptors in NIH-3T3 cells transformed by c-met protooncogene.

We have previously reported that c-met protooncogene, a member of a new class of receptor tyrosine-kinase gene family, is transforming when overexpressed in NIH-3T3 cells. In this paper, we report that the c-met protooncogene-transformed cells proliferate in a serum- and growth factor-free medium and exhibit constitutive tyrosine phosphorylation of several cellular proteins including the met protooncogene-encoded p145 and p185. Further investigations revealed platelet-derived growth factor (PDGF)-independent phosphorylation of PDGF-beta receptors in the transformed cells. Phosphoamino acid analysis revealed phosphorylation of PDGF receptors at tyrosine and serine residues. The PDGF receptor phosphorylation is unlikely to occur via autocrine production of PDGF since we could not detect PDGF activity both at the RNA level and at a functional protein level. Additionally, phospholipase C-gamma (PLC-gamma) a substrate of activated PDGF receptors, was found to be physically associated with PDGF receptors in the absence of PDGF stimulation in transformed cells. Furthermore, PDGF receptors coimmunoprecipitated along with PLC-gamma. Taken together, our results demonstrate a PDGF-independent phosphorylation and activation of PDGF-beta receptor in NIH-3T3 cells transformed by c-met protooncogene.

Inhibition of the epidermal growth factor receptor tyrosine kinase activity by leflunomide.

The active metabolite of leflunomide, A77 1726 inhibits the proliferation of a variety of mammalian cell lines in culture. Epidermal growth factor (EGF)-dependent proliferation is inhibited by A77 1726 at an effective dose of 30-40 microM. A77 1726 appears to directly inhibit the EGF receptor tyrosine-specific kinase activity both in intact cells and purified EGF receptors at the same effective dose. These data suggest that leflunomide inhibits cellular proliferation by the inhibition of tyrosine-specific kinase activities.

Poor reliability of the first meal tolerance test.

The poor reproducibility of oral glucose tolerance test (OGTT) has been known for a long time. Some recent reports indicate that postprandial glycaemia achieved during the test is likely to be higher on the first occasion than on subsequent visits. We have analysed our recent data on meal tolerance tests (MTT) from this angle. Fifteen healthy subjects and 9 subjects having NIDDM were administered two essentially identical meals one or two weeks apart. In case of healthy subjects, the absolute as well as incremental postprandial glycaemia achieved at 0.5 h and 1.0 h on the first visit was significantly higher (P < 0.05) than on the subsequent visit. The effect of visit was insignificant in case of NIDDM subjects. The effect observed in healthy subjects may be due to the release of adrenaline during the first visit brought about by apprehension. In NIDDM subjects the apprehension is likely to be much less because of their having undergone such tests in the past. Hence a single casual OGTT or MTT is unreliable as a diagnostic tool in borderline cases of impaired glucose tolerance test. The test needs to be repeated at least once more to eliminate false positives.