Search

A case report of a 73-year-old man admitted in the intensive care unit with acute renal failure and lithium toxicity is reported. Lithium is a gold standard drug for bipolar disorder. It has a narrow therapeutic index and requires blood level monitoring frequently. Hemodialysis is the last resort in management of lithium toxicity but in between high rebound levels during the dialysis result in persistent CNS toxicity.

Background: Acne and scabies are significant skin diseases and treatment of which carries major economic burden in Indian scenario. We planned study to compare safety, efficacy, and economy of treatment modalities of scabies for permethrin, benzyl benzoate, and ivermectin and acne for doxycycline and azithromycin. Hence, we can provide better treatment option for acne and scabies based on cost-effectiveness, efficacy, and safety. Aims and Objectives: This study aims to study therapeutic efficacy and cost-effective analysis of treatment in acne vulgaris and scabies. Materials and Methods: A multicentric, prospective observational study was carried out with patients attending the outpatient department of 32 health-care centers of Wardha district. One hundred and forty-eight patients of acne and 124 patients were screened, of which 108 patients of acne and 120 patients of scabies were analyzed for therapeutic efficacy. Of 120 scabies patients, 52 patients took benzyl benzoate lotion, 48 patients received permethrin cream, and 20 patients received tablet ivermectin. In acne, 60 patients received tablet azithromycin and 48 patients received tablet doxycycline. Cost-effective analysis was done. Results: In scabies, efficacy was near 93% for all therapeutic agents, but benzyl benzoate (INR 15.01 per case) and ivermectin (INR 16.07 per case) are more cost effective than permethrin (INR 21.55 per case). In acne, azithromycin (62.2%) and doxycycline (60%) showed similar efficacy, but doxycycline (INR 112 per case) is more cost effective than azithromycin (INR 216 per case). Conclusion: Therapeutic efficacy was similar for all therapeutic agents in both acne and scabies. Benzyl benzoate and ivermectin are more cost effective than permethrin in scabies. In acne, doxycycline is more cost effective than azithromycin.

An application of aminoacetaldehyde dialkoxy acetal to introduce an amino fuctionality in the 6 and/or 11 position of the naphthacenetrione ring system, resulting in key intermediates to aminated anthracyclines, is described.

An efficient and simple preparation of α - substituted aminoanthraquinones using 2,2-dialkoxyethylamines is described.

Chlorpromazine N-oxide, fluphenazine N 4 ’-oxide, prochlor-perazine N 4 ’-oxide, sulforidazine N -oxide, and trifluoperazine N 4 ’-oxide were synthesized by oxidation of the designated nitrogen atom in the N- 10 side chain of the respective parent drug with 3-chloroperoxybenzoic acid. In the case of trifluoperazine, a stepwise increase in the amount of oxidant yielded the N 1 ,N 4 -dioxide and N 1 ’, N 4 ’,S-trioxide. The N’,S- dioxides of chlorpromazine and sulforidazine were obtained by hydrogen peroxide oxidation of the appropriate parent drug.

An application of aminoacetaldehyde dialkoxy acetal to introduce an amino fuctionality in the 6 and/or 11 position of the naphthacenetrione ring system, resulting in key intermediates to aminated anthracyclines, is described.

Background: Drug-induced hepatotoxicity is a potentially serious adverse effect of antituberculosis treatment (ATT) regimens containing isoniazid, rifampicin and pyrazinamide. Many in vitro and in vivo studies revealed that honey possess antioxidant property and hepotoprotective property but there is no systematic work available to test the effect of honey on antitubercular drugs induced hepatotoxicity in rats. Hence present study was carried out to explore the prophylactic and therapeutic effect of honey with its antioxidant activity against hepatotoxicity induced by antitubercular drugs (Isoniazid, Rifampicin and Pyrazinamide) in albino rats. Methods: Hepatotoxicity in rats treated with antitubercular drugs (Isoniazid, Rifampicin and Pyrazinamide) was studied by assessing parameters such as Serum alanine aminotransferase (ALT), Serum aspartate aminotransferase (AST), Serum total protein, Serum Malondialdehyde (MDA) and Serum Superoxide dismutase activity (SOD). The effect of Honey as co-administration and administration after establishment of hepatotoxicity on above parameter was investigated. These biochemical observations were supplemented by Histopathological examination of liver. Results: Honey significantly reversed changes in serum levels of AST, ALT, MDA, SOD, total protein and also histopathological changes produced by Antitubercular drugs. It was found that honey significantly prevented as well as reversed Antitubercular drugs induced hepatotoxicity and antioxidant activity. Conclusions: The results of present study show that honey has significant prophylactic and therapeutic value against antitubercular drugs induced hepatotoxicity.

Two new procedures are described for the preparation of di- and tetra-deuterated 10-[[3-[4-(2-hydroxyethyl)-1-piperazinyl]propyl]]-2-trifluoromethyl-10H-phenothiazine (fluphenazine). Deuterium was introduced in either the 1- or the 1- and 3-positions of the propyl side chain by reduction with deuterated borane in tetrahydrofuran of the appropriately substituted N-10 amide or amido ester. The isotopic purity of the synthesized deuterated products was greater than 99%.

The results of adiabatic compressibility measurements for two copolymers, acrylic acid-vinyl pyrrolidone (AA—VP) and N-dimethylaminoethyl methacrylate-vinyl pyrrolidone (DAM—VP), in three different solvents, namely, water, methanol, and dioxane, have been described. The molecular weight of copolymers was determined by the light scattering method and the IR and NMR spectra of the polymers and copolymers were examined to establish that the alternating acrylic acid–vinyl pyrrolidone and N-dimethylaminoethyl methacrylate–vinyl pyrrolidone structure exists in the copolymers. The AA—VP copolymer behaves as a slightly weaker acid than the homopolymer of acrylic acid, while DAM—VP copolymer is very feebly basic and has the same strength as that of the homopolymer of N-dimethylaminoethyl methacrylate. The reduced viscosity for the two copolymers in aqueous solution is very low (∼0.08 dL/g for AA—VP copolymer). In methanol solution AA—VP and DAM—VP copolymers show a decrease of oK°2 and oV°2 by 61.6 × 10−4 cc/bar/mol and 8.0 cc/mol, and 191.0 × 10−4 cc/bar/mol and 20.0 cc/mol, respectively, over that of the values of aqueous solution. The void space around the solute is smaller in methanol than in water, and accordingly this decrease has been attributed to geometric effect. Only one copolymer, DAM—VP is soluble in dioxane, and the values are seen to have increased in this solution by 71.0 × 10−4 cc/bar/mol and 18.7 cc/mol, respectively, compared to the values obtained from aqueous solution. The experimentally determined oK°2 and oV°2 for AA—VP and DAM—VP copolymer are 0.6 × 10−4 cc/bar/mol, and 102.4 cc/mol and −61.0 × 10−4 cc/bar/mol, 94.4 cc/mol, respectively, in aqueous solution, and −12.0 × 10−4 cc/bar/mol, 211.0 cc/mol and −203.0 × 10−4 cc/bar/mol, 191.0 cc/mol, respectively, in methanol solution. In dioxane solution the values for DAM—VP copolymer are 59.0 × 10−4 cc/bar/mol and 229.7 cc/mol, respectively. These experimentally determined values for AA—VP copolymer show an increase by 0.04 × 10−4 cc/bar/mol, 4.4 cc/mol and 28.3 × 10−4 cc/bar/mol, 8.0 cc/mol in aqueous and methanol solution, respectively, compared to calculated values determined on the basis of no interaction between acid and the pyrrolidone group. In contrast, the DAM—VP copolymer shows a decrease of 27.6 × 10−4 cc/bar/mol and 10.3 cc/mol, 149.3 × 10−4 cc/bar/mol and 20.2 cc/mol, and 23.0 × 10−4 cc/bar/mol and 4.1 cc/mol in aqueous, methanol, and dioxane solutions, respectively. In aqueous solution these differences between calculated and observed values have been attributed to a change of water structure around the copolymer chain. A similar effect is responsible for the difference of the values in the methanol solution also. In the dioxane solution the difference is rather small, and the solvent structure has probably not altered much due to the presence of the DAM unit in the chain.

For the separate development of radioimmunoassay procedures for thioridazine and its two major active metabolites, mesoridazine and sulforidazine, three haptens, respectively, 2-methylthio-, 2-methylsulfinyl-, and 2-methylsulfonyl-substituted 10-[2-[1-(2-carboxyethyl)-2-piperidinyl]ethyl]-10H-phenothiazine, were synthesized and characterized. Thioridazine hapten was coupled to bovine serum albumin, whereas the haptens for mesoridazine and sulforidazine were coupled to porcine thyroglobulin. The number of hapten residues per mole of carrier protein was determined in each case by an ultraviolet spectrophotometric method. Polyclonal antibodies to each hapten-protein conjugate were obtained in rabbits, and titers of the antisera were checked by evaluating their binding characteristics to the appropriate tritiated analyte. A hapten for the ring sulfoxide metabolite of thioridazine was also synthesized.

The adiabatic compressibility of two ionic polymers; namely, poly(acrylic acid) (PAA) and poly(N-dimethylaminoethyl methacrylate) (PDAM) in methanol and dioxane solutions and of a nonionic polymer, poly(vinyl pyrrolidone) (PVP) in aqueous, methanol, and dioxane solutions has been studied. The φV2 and φK2 values for the three polymers and their corresponding monomers in methanol and dioxane solutions are found to be concentration independent. There is a marked difference in φK02 and φV02 values between monomer and polymer in all three solvents. In aqueous solution, the difference in φV02 is, on an average, 16.1 cm3/mol, while in methanol and dioxane solution, the same is 24.0 and 20.5 cm3/mol (average), respectively. All three monomers in dilute aqueous solution show a contraction of volume and decrease of adiabatic compressibility which are comparatively small in methanol and dioxane solutions. The φV02 for PAA, PDAM, and PVP were found to have increased by 0.8, 11.0, and 1.5 cm3/mol, respectively, in dioxane solution over that of the value of the aqueous solution. It is interesting to note that in methanol solution, PAA, PDAM, and PVP show a decrease of φK02 and φV02 values by 68.8 cm3/bar/mol and 8.2 cm3/bar/mol, 32.7 cm3/bar/mol, and 4.3 cm3/mol, and 36.6 cm3/bar/mol and 5.8 cm3/mol, respectively, compared to the values obtained from aqueous solution. This has been ascribed to geometric effect since the void space around the molecules is smaller in methanol than in water.

A series of anthraquinonyl glucosaminosides (10a-e) were synthesized by Koenigs-Knorr glycosidation of the corresponding aglycones (11a-e) with bromo sugar 12 followed by saponification. These glycosides were intended to serve as models to study the role played by the hydroxyl substituents on the aglycone portion of the antitumor anthracycline antibiotics. Superoxide generation as measured in rat heart sarcosomes was found to increase with the addition of successive hydroxyl groups to the anthraquinone nucleus. The 1,8-dihydroxy pattern was determined to generate significantly less superoxide than the 1,4-dihydroxy pattern. Hydroxyl substitution was also observed to stabilize the complex formed between the anthraquinones and DNA and was required for antibacterial activity against a number of Gram-positive organisms.

Antisera to fluphenazine sulfoxide were raised in New Zealand white rabbits to an immunogen synthesized by covalent linkage of bovine serum albumin to 10-[[3-[4-(4-carboxybutyl)-1-piperazinyl] propyl]]-2-trifluoromethyl-10H-phenothiazine 5-sulfoxide. With use of an antiserum, a radioimmunoassay for fluphenazine sulfoxide was developed that is able to quantitate 0.156 ng ml-1 using only a 200 microliter plasma sample with a coefficient of variation less than 5%. The antiserum had negligible cross-reactivities to fluphenazine (less than 1%) and its important metabolites, such as fluphenazine N4'-oxide (1%), 7-hydroxyfluphenazine (less than 1%), and N4'-deshydroxy-ethylfluphenazine (1%). The cross-reactivities with structurally similar phenothiazine 5-sulfoxides, such as those of trifluoperazine, prochlorperazine, perphenazine, and N4'-deshydroxyethylfluphenazine, were considerable, such that the antiserum can be used to develop a quantitative radioimmunoassay for any of these compounds. The reported radioimmunoassay was found to be suitable and adequate to quantitate fluphenazine sulfoxide in the plasma of patients treated with oral or intramuscular fluphenazine.

A series of anthraquinonyl glucosaminosides (10a-e) were synthesized by Koenigs-Knorr glycosidation of the corresponding aglycones (11a-e) with bromo sugar 12 followed by saponification. These glycosides were intended to serve as models to study the role played by the hydroxyl substituents on the aglycone portion of the antitumor anthracycline antibiotics. Superoxide generation as measured in rat heart sarcosomes was found to increase with the addition of successive hydroxyl groups to the anthraquinone nucleus. The 1,8-dihydroxy pattern was determined to generate significantly less superoxide than the 1,4-dihydroxy pattern. Hydroxyl substitution was also observed to stabilize the complex formed between the anthraquinones and DNA and was required for antibacterial activity against a number of Gram-positive organisms.