Effect of trimethoprim-sulphamethoxazole on vibrio clearance in cholera (El Tor): a comparative study

The efficacy of trimethoprim-sulphamethoxazole (TMP-SMX) has been compared with that of tetracycline and chloramphenicol in 175 bacteriologically confirmed cases of cholera admitted to the Infectious Diseases Hospital Delhi. Vibrio cholerae, biotype El Tor, serotype ogawa, were isolated from all the patients. TMP-SMX showed greater in vitro inhibition and earlier eradication from the intestinal tract and is recommended as a suitable vibriocidal agent against cholera.     

Mutagenic activation of 4-aminobiphenyl and its N-hydroxy derivatives by microsomes from cultured human uroepithelial cells

Activation of the human bladder carcinogen 4-aminobiphenyl (ABP)and its N-hydroxy derivatives was investigated using lysatesand subcellular enzyme preparations from cultured human uroepithelialcells (HUC). Mutagenic activation was determined using Salmonellatyphimurium strains TA98; TA98/1,8-DNP₆, a derivative deficientin acetyl coenzyme A:N-hydroxyarylamine O-acetyltransferase(OAT); and YG1024, a derivative of TA98 with elevated OAT activityand enhanced sensitivity to mutation by N-hydroxyarylamines.Mutagenicity of ABP catalyzed by HUC microsomes was detectedin YG1024 but not hi the parent strain TA98. HUC microsomesalso catalyzed the mutagenic activation of N-hydroxy-4-acetylaminobiphenyl(N-OH-AABP) and the relative sensitivity of the tester strainswas YG1024 > TA98 > TA98/1,8-DNP₆, indicating N-hydroxy-4-aminobiphenyl(N-OH-ABP) as the mutagenic intermediate. In contrast, the mutagenicactivity of N-acetoxy-4-acetylaminobiphenyl incubated with HUCmicrosomes was approximately equal in TA98 and YG1024, and mayinvolve N-acetoxy-4-aminobiphenyl (N-OAc-ABP) as the intermediate.High pressure liquid chromatography (HPLC) of the DNA hydrolysateobtained after incubation of [³H]N-OH-ABP with YG1024, showedN-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-ABP) as the primaryadduct, based on mobility of the radioactivity in comparisonwith the synthetic standard. Additionally, HUC microsomes catalyzedthe binding of [³H]N-OH-ABP to RNA in the presence of 4-acetylaminobiphenyl(AABP), N-OH-AABP and acetyl coenzyme A as acetyl donors, andthis binding was blocked by paraoxon. The hydrolysate obtainedfrom incubation of DNA with [³H]N-OH-ABP and HUC microsomes,with AABP as acetyl donor, revealed the formation of dG-ABPadduct. ³²P-post-labeling of adducted DNA from N-OH-ABP, N-OH-AABPand N-OAc-AABP showed similar adduct profiles, suggesting thatthe aryl nitrenium ion, arising from N-OAc-ABP, might be thereactive species responsible for the mutagenic activity. ¹To whom correspondence should be addressed     

4D-CT Lung registration using anatomy-based multi-level multi-resolution optical flow analysis and thin-plate splines

Purpose

   The accuracy of 4D-CT registration is limited by inconsistent Hounsfield unit (HU) values in the 4D-CT data from one respiratory phase to another and lower image contrast for lung substructures. This paper presents an optical flow and thin-plate spline (TPS)-based 4D-CT registration method to account for these limitations.

Methods

   The use of unified HU values on multiple anatomy levels (e.g., the lung contour, blood vessels, and parenchyma) accounts for registration errors by inconsistent landmark HU value. While 3D multi-resolution optical flow analysis registers each anatomical level, TPS is employed for propagating the results from one anatomical level to another ultimately leading to the 4D-CT registration. 4D-CT registration was validated using target registration error (TRE), inverse consistency error (ICE) metrics, and a statistical image comparison using Gamma criteria of 1 % intensity difference in \(2\,\hbox {mm}^{3}\) window range.

Results

   Validation results showed that the proposed method was able to register CT lung datasets with TRE and ICE values \(<\) 3 mm. In addition, the average number of voxel that failed the Gamma criteria was \(<\) 3 %, which supports the clinical applicability of the propose registration mechanism.

Conclusion

   The proposed 4D-CT registration computes the volumetric lung deformations within clinically viable accuracy.     

Mutagenicity of 3,4-diphenyl-5-nitrofuran analogs in Salmonella typhimurium

A new series of chemicals comprising eight different 3, 4-di-phenylsubstitutedfuran analogs, namely, methyl-3, 4-di-phenyl-2-furoate, methyl-3,4-diphenyl-5-nitro-2-furoate, 3, 4-diphenyl-5-nitro-2-furoicacid, 3, 4-diphenyl-5-nitro-2-acetylfuran, 3, 4-diphenyl-5-nitro-2-bromoacetylfuran,2-amino-4-(3, 4-diphenyl-5-nitro-2-furyl)thiazole, 2-acetyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole and 2-formyl-amino-4-(3,4-diphenyl-5-nitro-2-furyl)thiazole were synthesized and theirmutagenic activities tested in Salmonella typhi-murium. Thestructure—activity relationship studies revealed thatfor mutagenic activity the nitro group is essential and thatthe potency of activity is greatly altered by the nature ofthe substituent at the 2-position of the furan ring. The mutagenicactivities of these chemicals were generally much higher inTA100 compared to TA98. The relative order of activities for2-substituted, 3, 4-diphenyl-5-nitrofurans were COOCH₃ >COCH₂BR > COCH₃ > COOH in S. typhi-murium TA100. 3, 4-Diphenyl-5-nitro-2-bromoacetylfuranwas equally active in nitroreductase-proficient (TA98, TA100)and in nitroreductase-deficient (TA98NR, TA100NR) strains. Incontrast, the acetyl and carboxymethyl ester analogs were relativelyless active in nitroreductase-deficient strains. Mutagenic activitiesof 3, 4-diphenyl-substituted furylthiazoles in comparison withthe unsubstituted analogs of N-[4-(5-nitro-2-furyl)-2-thiazolyl]-formamide,N-[4-(5-nitro-2-furyl)-2-thiazolyl]-acetamide and 2-amino-4-(5-nitro-2-furyl)thiazolerevealed that the phenyl groups drastically reduced their mutagenicactivities. However, the relative order of activities formylamino<< acetylamino > amino were the same between phenyl-substitutedand unsubstituted analogs.     

Bacterial vaginosis in female sex workers in Chennai, India

Bacterial vaginosis (BV) causes obstetric and gynaecological complications and non-chlamydial/non-gonococcal pelvic inflammatory disease and has been shown to be associated with the risk of acquiring HIV and herpes simplex (HSV)-2 infections. This study investigated both the prevalence of BV and its association with STDs among 582 female sex workers living in Chennai, South India. Blood, vaginal and endocervical swabs were tested for HSV-2, HIV, Treponema pallidum, BV, Chlamydia trachomatis, Neisseria gonorrhoea and Trichomonas vaginalis. The vaginal swabs collected were Gram's stained and analysed for BV by Nugent's scoring criteria. Of the women studied, 45% (95% CI, 40.6-48.7) were positive, 39.5% (95% CI, 35.5-43.5) were negative and 16% (95% CI, 12.8-18.7) were intermediate for BV. Bacterial vaginosis positivity was directly related to concurrent infection with HSV-2 (RR 1.3, AR 12, P = 0.00), T vaginalis (RR 1.5, AR 10, P = 0.01) T. pallidum (RR 2.8, AR 16, P = 0.00) and HIV (RR 4.1, AR 52, P = 0.01). Future studies are needed to focus on the risk factors for BV.     

The tumor suppressor PP2A is functionally inactivated in blast crisis CML through the inhibitory activity of the BCR/ABL-regulated SET protein

The oncogenic BCR/ABL kinase activity induces and maintains chronic myelogenous leukemia (CML). We show here that, in BCR/ABL-transformed cells and CML blast crisis (CML-BC) progenitors, the phosphatase activity of the tumor suppressor PP2A is inhibited by the BCR/ABL-induced expression of the PP2A inhibitor SET. In imatinib-sensitive and -resistant (T315I included) BCR/ABL+ cell lines and CML-BC progenitors, molecular and/or pharmacological activation of PP2A promotes dephosphorylation of key regulators of cell proliferation and survival, suppresses BCR/ABL activity, and induces BCR/ABL degradation. Furthermore, PP2A activation results in growth suppression, enhanced apoptosis, restored differentiation, impaired clonogenic potential, and decreased in vivo leukemogenesis of imatinib-sensitive and -resistant BCR/ABL+ cells. Thus, functional inactivation of PP2A is essential for BCR/ABL leukemogenesis and, perhaps, required for blastic transformation.     

Sedation in pediatric patients

Sedation is being used increasingly in children to allay anxiety and discomfort. Sedation can also increase the efficiency of performing both diagnostic and therapeutic procedures in children. There are a wide array of available sedation methods that are used by radiologists, gastroenterologists, hematologists/oncologists and emergency room physicians everyday. Indiscriminate use of sedatives has led to seizures, respiratory arrests and death in a variety of practice settings. With improved monitoring capability, more potent drugs and better understanding of the pharmacokinetics in children, it is possible to provide batter care.