Evaluation of clinical outcomes in neuropathic pain with combinations of anti-neuropathic drugs

Background: Much of the pharmacological treatment modalities especially individual drugs for treating neuropathic pain have unwanted side effects, multiple day to day dosing, modest efficacy of topical treatments, and their local side effects. Combination drug regimen has the advantage of offering relatively better pain relief at lower drug doses and lesser side effects.Methods: The study was conducted in the Department of Neurology at NRI General Hospital, Guntur. The patients who met the inclusion and exclusion criteria were enrolled and assigned into 3 groups of the study drug combinations. The baseline characteristics and post interventional scores of Toronto Clinical Scoring System (TCSS), visual analogue scale (VAS), Hamilton Anxiety Rating Scale (HAM-A), Hamilton Depression Rating Scale (HAM-D) and Medical outcome of sleep scale (MOS) and were analyzed using t test and mean difference.Results: A statistically significant reduction in neuropathic pain in all the three groups was found. The mean difference between the baseline and post interventional scores of TCSS and VAS of group I, II and III were 2.97, 2.75, and 1.97; 2.32, 1.12, and 0.95 respectively. There was a statistically significant improvement of HAM-A in all the three groups, HAM-D and MOS sleep scale were found significant only in group II.Conclusions: The study findings revealed that all the three drug combinations were effective in the management of neuropathic pain with pregabalin and oxcarbazepine combination being better with respect to efficacy and tolerability. Regarding the treatment of depression and sleep disturbances associated with NP pregabalin and duloxetine was more effective

Vitamin D Receptor FokI, ApaI, and TaqI Polymorphisms in Lead Exposed Subjects From Saudi Arabia

Vitamin D receptor (VDR) gene polymorphisms were reported to influence blood lead levels (BLL) and the response of subjects to the symptoms of lead toxicity. However, no studies have been conducted in the Saudi Arabian population which has unique ethnicity and socio-demographic features. This study examined the polymorphisms in exon 2 (allele 1) and intron 8 (allele 2 and allele 3) of VDR gene and their relation to BLLs. As per the CDC guidelines, the recruited lead-exposed workers (N = 130) were categorized to two groups viz., low BLL group (<10 μg/dL) and high BLL group (>10 μg/dL). The low BLL group had a mean BLL of 4.37 μg/dL, while the high BLL group had levels of 18.12 μg/dL (p < 0.001). Overall, the genetic variants, TC and CC in the VDR FokI were significantly associated with a risk of lead toxicity and the allele “C” was a risk factor (p = 0.00026). Furthermore, the TT genotype of VDR ApaI significantly increased the risk of developing lead poisoning (p = 0.0006). The VDR TaqI SNP was not significantly associated with lead toxicity. The highest BLLs for VDR FokI-CC, VDR ApaI-GG, and VDR TaqI-TT genotypes from High BLL group were 18.42, 15.26, and 18.75 μg/dL, respectively. Older age (51–60 years) was found to be a significant confounding factor for BLLs (p = 0.012). Additional studies in larger sample sizes are needed to firmly establish the role of VDR genotypes and genetic susceptibility to lead poisoning

A simplified Cadogan’s approach to synthesis of new isoxazolyl indazoles

1591-1596Isoxazolyl Schiff bases have been prepared from the corresponding amines by reaction with 2-nitrobenzaldehydes.These nitro compounds undergo de-oxygenative cyclization to give indazoles via nitrenes on heating with triethyl phosphite in acetonitrile. Isoxazolyl indazoles have also been synthesized in a one-pot reaction

Synthesis of novel isoxazolyl 1,3,5-benzoxadiazocine-4-thiones as possible biodynamic agents

1753-1758Synthesis of novel isoxazolyl 1,3,5-benzoxadiazocine-4-thiones 5 has been accomplished by condensation of 4-amino-3-methyl-5-styrylisoxazole 1 with salicylaldehydes, followed by reduction, treatment with arylisothiocyanates and subsequent ring closure in the presence of formaldehyde. The methodology used in this synthesis is the first approach of its kind towards the synthesis of title compounds

Synthesis of 1,3,5-triazinane-2-thiones and 1,3,5-oxadiazinane-4-thiones linked with isoxazoles

119-122 Trimolecular condensation of N-(3,5-dimethyl-4-isoxazolyl)-N'-arylthioureas 2 obtained from 1 by reaction with aryliso­thiocyanates, with aqueous formaldehyde and primary amines in toluene under reflux leads to 5-alkyl-1-(3,5-dimethyl-4-iso­xa­zolyl)-3-aryl-hexahydro-1,3,5-triazinane-2-thiones 3 in excellent yields. Condensation of 2 with aqueous formaldehyde under similar condition provides isoxazolyl 1,3,5-oxadiazinane-4-thiones 4. </smarttagtype

Synthesis and in vitro study of novel isoxazolyl benzoimidazolyl benzamides, acrylamides and propionamides as antimicrobial agents

1284-1290A series of novel 2/3 (1H-benzoimidazol-2-yl)-N-(5-methyl-3-isoxazolyl)-benzamides, acrylamides and propionamides have been synthesized and the antimicrobial activities are evaluated against two Gram-positive and two Gram-negative bacteria and two plant-pathogenic fungi. Some of the synthesized compounds have showed superior in vitro activities as compared to the standard drugs

Haplotype Analyses of DNA Repair Gene Polymorphisms and Their Role in Ulcerative Colitis

<div><p>Ulcerative colitis (UC) is a major clinical form of inflammatory bowel disease. UC is characterized by mucosal inflammation limited to the colon, always involving the rectum and a variable extent of the more proximal colon in a continuous manner. Genetic variations in DNA repair genes may influence the extent of repair functions, DNA damage, and thus the manifestations of UC. This study thus evaluated the role of polymorphisms of the genes involved in DNA repair mechanisms. A total of 171 patients and 213 controls were included. Genotyping was carried out by ARMS PCR and PCR-RFLP analyses for <i>RAD51</i>, <i>XRCC</i>3 and <i>hMSH2</i> gene polymorphisms. Allelic and genotypic frequencies were computed in both control & patient groups and data was analyzed using appropriate statistical tests. The frequency of ‘A’ allele of <i>hMSH</i>2 in the UC group caused statistically significant increased risk for UC compared to controls (OR 1.64, 95% CI 1.16–2.31, <i>p</i> = 0.004). Similarly, the CT genotype of <i>XRCC</i>3 gene was predominant in the UC group and increased the risk for UC by 1.75 fold compared to controls (OR 1.75, 95% CI 1.15–2.67, <i>p</i> = 0.03), further confirming the risk of ‘T’ allele in UC. The GC genotype frequency of <i>RAD</i>51 gene was significantly increased (<i>p</i> = 0.02) in the UC group (50.3%) compared to controls (38%). The GC genotype significantly increased the risk for UC compared to GG genotype by 1.73 fold (OR 1.73, 95% CI 1.14–2.62, <i>p</i> = 0.02) confirming the strong association of ‘C’ allele with UC. Among the controls, the SNP loci combination of <i>hMSH</i>2:<i>XRCC</i>3 were in perfect linkage. The GTC and ACC haplotypes were found to be predominant in UC than controls with a 2.28 and 2.93 fold significant increase risk of UC.</p></div

Haplotype association with response.

<p>Haplotype association with response.</p