Threshold sensitivity of taste perception and the role of saliva and Zinc level in some physiological & pathological conditions

Background: Decreased taste acuity to the four basic tastes is closely related to health problems (diseases & medications), aging, and smoking. This study aimed to determine taste detection and recognition thresholds to the four basic tastes in some physiological and pathological conditions, determine saliva flow rate, serum and saliva zinc levels in these groups. Objective and Methods: The study includes 218 individuals (35–80) years old divided into six groups; the control, aging (subjects over 60 years), smokers, diabetics, haemodialysis patients and hypertensive patients on chronic use of captopril.The taste detection and recognition thresholds of sweet, salty, sour and bitter tastes, saliva flow rate were determined. Zinc concentration was assessed in serum and saliva spectrophotometricaly. Results: The results showed a significant increase in the taste detection and recognition thresholds of the four basic tastes of all groups than in the control, except the salty taste thresholds of the haemodialysis group and the salty taste detection threshold of the diabetics. Saliva flow rates, serum and saliva zinc levels decreased significantly at p<0.001 in study groups as compared to the control group. Conclusions:The taste acuity was impaired in aged subjects, smokers, diabetics, haemodialysis patients, and hypertensive patients on chronic use of captopril. Decreased saliva flow rate and saliva zinc concentration could be causative factors for hypogeusia

4-(2-Methoxyphenyl)piperazin-1-ium 6-chloro-5-isopropyl-2,4-dioxopyrimidin-1-ide

In the cation of the title salt, C11H17N2O+.C7H8ClN2O2 -, the piperazine ring adopts a distorted chair conformation and contains a positively charged N atom with quaternary character. Its mean plane makes a dihedral angle of 42.36 (8)� with the phenyl ring of its 2-methoxyphenyl substituent. The 2,4-dioxopyrimidin-1-ide anion is generated by deprotonation of the N atom at the 1-position of the pyrimidinedione ring. Intramolecular C—H...O hydrogen bonds generate S(6) ring motifs in both the cation and the anion. In the crystal, N—H...O, N—H...N and C—H...O hydrogen bonds are also observed, resulting in a twodimensional network parallel to the ab plane. The crystal stability is further consolidated by weak C—H...n interactions

3-(Adamantan-1-yl)-4-benzyl-1H-1,2,4-triazole-5(4H)-thione

The title compound, C19H23N3S, is a functionalized triazoline-3-thione derivative. The benzyl ring is almost normal to the planar 1,2,4-triazole ring (r.m.s. deviation = 0.007 A°) with a dihedral angle of 86.90 (7)°. In the crystal, molecules are linked by pairs of N—H...S hydrogen bonds, forming inversion dimers that enclose R2/2(8) loops. The crystal packing is further stabilized by weak C—H...n interactions that link adjacent dimeric units into supramolecular chains extending along the a-axis direction

Crystal structure of 2-[(4-bromobenzyl)thio]-5-(5-bromothiophen-2-yl)-1,3,4-oxadiazole, C₁₃H₈Br₂N₂OS₂

C13H8Br2N2OS2, monoclinic, Pc (no. 7), a = 13.4050(4) angstrom, b = 4.7716(1) angstrom, c = 11.7303(4) angstrom, beta = 105.885( 3)degrees, V = 721.66(4) angstrom(3), Z = 2, R-gt(F) = 0.0294, wR(ref) (F-2 = 0.0808, T = 160K

Effect of Berberine on in vitro metabolism of Sulfonylureas: a herb-drug interactions study

Rationale: Patients with type 2 diabetes may co-ingest herbal and prescription medicine to control their blood sugar levels. Competitive binding of drug and herb may mutually affect their metabolism. This can alter the level of drug and its kinetics in the body, potentially causing toxicities or loss of efficacy. Understanding how metabolism of sulfonylureas like glyburide and gliclazide can be affected by the presence of berberine and vice versa can provide valuable information on the possible risk of toxicities caused by co-ingestion of drugs. Methods: Berberine and sulfonylureas (glyburide and gliclazide) were co-incubated with rat liver microsomes in the presence of NADPH regenerating system. The metabolites of berberine and sulfonylureas were analysed using liquid chromatography with high resolution mass spectrometry in the positive ion mode. The role of individual isozymes in the metabolism of berberine, glyburide and gliclazide was investigated by using specific inhibitors. Results: In vitro metabolism of berberine lead to the formation of demethyleneberberine (B1a) and B1b through demethylenation. Berberrubine (B2a) and its isomer (B2b) was formed through demethylation. The isozymes CYP3A and CYP2D were found to be involved in the metabolism of berberine. In vitro metabolism of glyburide and gliclazide lead to the formation of hydroxylated metabolites. The isozymes CYP3A and CYP2C were found to be involved in the metabolism of glyburide. Gliclazide was metabolised by CYP2C. In vitro co-incubation of glyburide or gliclazide with berberine showed that each drugs metabolism was compromised as both share a common isozymes. A strong negative linear correlation of glyburide or gliclazide metabolites levels and the concentration of berberine confirmed the effect of berberine on the metabolism of sulfonylurea

Crystal structure of 3-[(4-benzylpiperazin-1-yl)methyl]-5-(thiophen-2-yl)- 2,3-dihydro-1,3,4-oxadiazole-2-thione

The title 1,3,4-oxadiazole-2-thione derivative, C18H20N4OS2, crystallized with two independent molecules (A and B) in the asymmetric unit. The 2-thienyl rings in both molecules are rotationally disordered over two orientations by approximately 180� about the single C—C bond that connects it to the oxadiazole thione ring; the ratios of site occupancies for the major and minor components were fixed in the structure refinement at 0.8:0.2 and 0.9:0.1 in molecules A and B, respectively. The 1,3,4-oxadiazole-2-thione ring forms dihedral angles of 7.71 (16), 10.0 (11) and 77.50 (12)� (molecule A), and 6.5 (3), 6.0 (9) and 55.30 (12)� (molecule B) with the major and minor parts of the disordered thiophene ring and the mean plane of the adjacent piperazine ring, respectively, resulting in approximately V-shaped conformations for the molecules. The piperazine ring in both molecules adopts a chair conformation. The terminal benzene ring is inclined towards the mean plane of the piperazine ring with N—C— C—C torsion angles of �58.2 (3) and �66.2 (3)� in molecules A and B, respectively. In the crystal, no intermolecular hydrogen bonds are observed. The crystal packing features short S� � �S contacts [3.4792 (9) A ° ] and �–� interactions [3.661 (3), 3.664 (11) and 3.5727 (10) A ° ], producing a threedimensional network

Adherence to Antiretroviral Therapy among HIV Infected Children Measured by Caretaker Report, Medication Return, and Drug Level in Dar Es Salaam, Tanzania.

Adherence to antiretroviral drugs in the treatment of paediatric HIV infection is complicated because of many factors including stigma and drug intake logistics. It is therefore important to identify children with non-adherence in order to intervene before they become at risk of developing treatment failure or drug resistance. The aim of this study was to determine the level of adherence to antiretroviral therapy (ART), measured by caretaker report, medication return and nevirapine plasma concentration. In addition, the association between level of adherence and patient's immune status was compared across the three methods of measuring adherence. This was a descriptive cross-sectional study involving HIV infected children aged 2-14 years, on nevirapine- based antiretroviral treatment for at least six months, attending care and treatment clinic in three municipal hospitals in Dar- Es- Salaam City. Eligible patients and their accompanying caretakers were consecutively enrolled after obtaining written informed consent. Structured questionnaires were administered to caretakers to assess patient's adherence by caretaker report and medication return whereas a single blood sample for CD4 cell count/percent and determination of nevirapine plasma concentration was taken from patients on the day of assessment. A total of 300 patients and accompanying caretakers were enrolled and the mean patient age (SD) was 8 (3) years. Caretakers' report and medication return showed good adherence (98% and 97%) respectively. However, the level of adherence assessed by nevirapine plasma concentration (85%) was significantly lower than caretaker report and medication return (p < 0.001). The agreement between nevirapine plasma concentration and medication return and between nevirapine plasma concentration and caretaker report was weak (k = 0. 131) (k = 0. 09) respectively. Nevirapine plasma concentration below 3 μg/ml was associated with immunosuppression (p = 0. 021) whereas medication return (>5% of prescribed doses) and caretaker reported missing more than one dose within 72 hours prior to interview were not associated with immunosuppression (p = 0. 474), (p = 0. 569) respectively. Lower adherence level observed using nevirapine plasma concentration and its association with immunological response supports the validity of the method and indicates that adherence data obtained from caretaker report and medication return may overestimate the true adherence in paediatric antiretroviral therapy

Pathways to Injury in Chronic Pancreatitis: Decoding the Role of the High-Risk SPINK1 N34S Haplotype Using Meta-Analysis

Background: The complex interactions between recurrent trypsin-mediated pancreatic injury, alcohol-associated pancreatic injury and SPINK1 polymorphisms in chronic pancreatitis (CP) are undefined. We hypothesize that CP occurs as a result of multiple pathological mechanisms (pathways) that are initiated by different metabolic or environmental factors (etiologies) and may be influenced differentially by downstream genetic risk factors. We tested this hypothesis by evaluating the differences in effect size of the high risk SPINK1 N34S haplotype on CP from multiple etiologies after combining clinical reports of SPINK1 N34S frequency using meta-analysis. Methods and Findings: The Pubmed and the Embase databases were reviewed. We studied 24 reports of SPINK1 N34S in CP (2,421 cases, 4,857 controls) using reported etiological factors as surrogates for pathways and multiple meta-analyses to determine the differential effects of SPINK1 N34S between alcoholic and non-alcoholic etiologies. Using estimates of between-study heterogeneity, we sub-classified our 24 studies into four specific clusters. We found that SPINK1 N34S is strongly associated with CP overall (OR 11.00; 95% CI: 7.59-15.93), but the effect of SPINK1 N34S in alcoholic CP (OR 4.98, 95% CI: 3.16-7.85) was significantly smaller than in idiopathic CP (OR 14.97, 95% C.I. = 9.09-24.67) or tropical CP (OR 19.15, 95% C.I. = 8.83-41.56). Studies analyzing familial CP showed very high heterogeneity suggestive of a complex etiology with an I2 = 80.95%. Conclusion: The small effect of SPINK1 N34S in alcoholic subjects suggests that CP is driven through a different pathway that is largely trypsin-independent. The results also suggest that large effect sizes of SPINK1 N34S in small candidate gene studies in CP may be related to a mixture of multiple etiologic pathways leading to the same clinical endpoint. © 2008 Aoun MD et al