Mostafa Hussein

Synthesis and antimicrobial activity of some new 1-alkyl-2-alkylthio-1,2,4-triazolobenzimidazole derivatives

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo-[2,3-a]benzimidazole-2-thione intermediate was reacted with one equivalent of alkyl halides to give the corresponding 2-alkylthio derivatives, which were further alkylated through the reaction with another one equivalent of different alkyl halides to afford the target compounds; 1-alkyl-2-alkylthio-1,2,4-traizolo[2,3-a]benzimidazoles. On the other hand, the 1,2-disubstituted derivatives with two identical alkyl substituents were prepared by the reaction of 1,2,4-triazolo[2,3-a]benzimidazole-2-thione with two equivalents of the alkyl halides. The structures of the new compounds were assigned by spectral and elemental methods of analyses. The synthesized compounds were tested for their antibacterial and antifungal activities. Most of the tested compounds proved comparable results with those ofampicillin andfluconazole reference drugs. The study indicated that, the antibacterial as well as the antifungal activities of the test compounds were improved with increase in the bulkiness of the introduced alkyl groups. Also, some active antibacterial compounds were tested for their antimycobacterial activity. All the test compounds showed equipotent antitubercular activity as that ofINH as a reference drug.

Selenium-Containing Heterocycles: Synthesis and Pharmacological Activities of Some New 4-Methylquinoline- 2(1H) Selenone Derivatives

Several selenolo[2,3‐b]quinolines and pyrimido[4′,5′:4,5]selenolo[2,3‐b]quinolines were prepared by annulations via reaction of NaSeH with 2‐chloro‐3‐cyano‐4‐methylquinoline 1 followed by reactions with aromatic aldehydes, cycloalkanones, and acetic anhydride. Spectroscopic (IR, 1H‐NMR, and MS) properties of the synthesized compounds are reported. Some selected compounds 5a, 7b, 7c, 8b–d, 9a, 11b, and 11d were investigated for their anti‐inflammatory and analgesic activities; in addition, the most active compounds were tested for their ulcerogenicity and acute toxicity. Moreover, some of the test compounds 7c, 9a, 11b, and 11d were screened for their antibacterial and antifungal activities.

Hormonal, follicular and endometrial dynamics in letrozole-treated versus natural cycles in patients undergoing controlled ovarian stimulation

The objective of this study was to compare letrozole-stimulated cycles to natural cycles in 208 patients undergoing intrauterine insemination (IUI) between July of 2004 and January of 2007. Group I (n = 47) received cycle monitoring only (natural group), Group II (n = 125) received letrozole 2.5 mg/day on cycle days three to seven, and Group III (n = 36) received letrozole 5 mg/day on cycle days three to seven. There were no differences between the groups in endometrial thickness or P4 on the day of hCG. Estradiol levels had higher variation in the second half of the follicular phase in both letrozole-treated groups compared to the control group. Estradiol per preovulatory follicle was similar in both letrozole cycles to that observed in the natural cycles. LH was lower on the day of hCG administration in the letrozole 2.5 mg/day group vs. the natural group. In summary, letrozole results in some minor changes in follicular, hormonal and endometrial dynamics compared to natural cycles. Increased folliculogenesis and pregnancy rates were observed in the letrozole-treated groups compared to the natural group. These findings need to be confirmed in larger, prospective studies.

An innovative lattice Boltzmann model for simulating Michaelis–Menten-based diffusion–advection kinetics and its application within a cartilage cell bioreactor

Lattice Boltzmann models (LBM) are rapidly showing their ability to simulate a lot of fluid dynamics problems that previously required very complex approaches. This study presents a LBM for simulating diffusion–advection transport of substrate in a 2-D laminar flow. The model considers the substrate influx into a set of active cells placed inside the flow field. A new innovative method was used to simulate the cells activity using the LBM by means of Michaelis–Menten kinetics. The model is validated with some numerical benchmark problems and proved highly accurate results. After validation the model was used to simulate the transport of oxygen substrates that diffuse in water to feed a set of active cartilage cells inside a new designed bioreactor.

Limited ovarian stimulation (LOS), prevents the recurrence of severe forms of ovarian hyperstimulation syndrome in polycystic ovarian disease

OBJECTIVES We aimed to test the possibility that LOS could be used to avoid the risk of occurrence of severe OHSS in PCOD patients with past history of severe OHSS in their previous IVF treatment. STUDY DESIGN A prospective study, with patients stood as their own controls. Twenty patients with history of severe OHSS in their previous IVF treatment were included in the study. The patients received LOS cycles during the six months period commencing January 1998, a full dose of human chorionic gonadotropin (10,000 IU) was administered when the leading follicle reached a mean diameter of 12 mm, and oocytes retrieval 36 h later was followed by intracytoplasmic sperm injection (ICSI) and embryo transfer. Signs and symptoms of severe OHSS were recorded. RESULTS All patients produced mature oocytes, achieved fertilisation and eight clinical pregnancies were diagnosed. None of the patients re-experienced the symptoms of severe OHSS, and none required hospitalisation. CONCLUSION We confirm that, in the studied group of patients, LOS helped in the prevention of the severe forms of OHSS in PCOD patients with past history of severe OHSS.

c-Jun NH2-terminal kinase inhibitor bentamapimod reduces induced endometriosis in baboons: an assessor-blind placebo-controlled randomized study

OBJECTIVE To test the hypothesis that the c-Jun NH2-terminal kinase (JNK) inhibitor (JNKI) bentamapimod (AS602801/PGL5001) can reduce induced endometriosis in baboons. DESIGN Prospective randomized placebo-controlled study. SETTING Nonhuman primate research center. ANIMAL(S) Twenty baboons each underwent four laparoscopies. Initial screening laparoscopy (L1) was followed after one rest cycle by an endometriosis-induction laparoscopy (L2). Fifty days after L2, the baboons were randomized just before staging laparoscopy (L3). Treatment lasted for 60 days, followed by a post-treatment staging laparoscopy (L4). INTERVENTION(S) Randomization before a 60-day treatment in four groups: daily placebo (n = 5), daily oral administration of 20 mg/kg JNKI (n = 5), concomitant daily oral administration of 20 mg/kg JNKI and 10 mg medroxyprogesterone acetate (MPA; n = 5), or subcutaneous administration of 3 mg cetrorelix every 3 days (n = 5). MAIN OUTCOME MEASURE(S) Type, surface area and volume of endometriotic lesions, and revised American Society for Reproductive Medicine score and stage were recorded during L3 and L4. Menstrual cycle length and serum hormonal concentration were recorded before and after treatment. RESULT(S) Compared with placebo, treatment with JNKI, JNKI + PMA, or cetrorelix resulted in lower total surface area and volume of endometriotic lesions. Remodeling of red active lesions into white lesions was observed more frequently in baboons treated with JNKI + MPA than in baboons treated with JNKI only. Menstrual cycle length and serum hormonal concentration were similar between placebo and JNKI groups. CONCLUSION(S) JNKI alone was as effective as JNKI + MPA or cetrorelix in reducing induced endometriosis in baboons, but without severe side effects or effect on cycle length or serum reproductive hormones.

Design and synthesis of some substituted thiazolo[3,2-a]pyrimidine derivatives of potential biological activities.

In continuation to our previous work, thiazolopyrimidines 2a–x were synthesized through intramolecular cyclization of 2-phenacylthio-dihydropyrimidine hydrobromides 1a–x using polyphosphoric acid. On the other hand, thiazolo[3,2-a]pyrimidine-3-one 3 was coupled with aryldiazonium salts or condensed with isatin to afford compounds 4a–c or 5, respectively. Chemical structure of the target compounds was substantiated by IR, FT-IR, 1H-, 13C and DEPT-13C NMR, MS as well as microanalyses. Moreover, the lipophilicity of the target compounds is expressed as Clog P. The antimicrobial screening of the test compounds 2a–x, 4a–c and 5 revealed moderate activity in comparison to reference drugs. Compounds 2a–c, 2e, 2o and 2v showed a gradual increase in their anti-inflammatory activity reaching its maximum at 5 h compared to indomethacin. Furthermore, the analgesic activity of compounds 2a–c, 2e, 2o and 2v revealed a maximum activity after 5 h of injection compared to aspirin and the LD50 of compounds 2e and 2v was determined.

Soluble tumor necrosis factor-alpha receptors in the serum of endometriosis patients

INTRODUCTION We examine serum levels sTNFR-I and sTNFR-II in endometriosis patients, and their role as biomarkers of endometriosis. MATERIAL AND METHODS Women were diagnosed with endometriosis during laparoscopy to investigate pelvic pain and/or infertility (N=62). Control group included women with pelvic pain and/or infertility, whose laparoscopy showed no abnormalities (N=55). Serum concentrations of sTNFR-I and sTNFR-II were measured using Bioplex Protein Array system. Non-parametric statistics were used. RESULTS Endometriosis patients had significantly higher levels of sTNFR-I than controls (257.46pg/ml, IQR=2.37-1048.92 versus 130.39pg/ml, IQR=0.99-361.1 respectively, P value=0.01). For TNFR-II, difference between women with (232pg/ml, IQR=0.0-624.4), and women without (132.93pg/ml, IQR=0.0-312.81) endometriosis was not significant (P value=0.05). Early stage endometriosis patients had significantly higher level of sTNFR-I (559.13, IQR=1.82-1289.86) and sTNFR-II (248.8, IQR=0-644.65) than control women (P value is 0.01 for TNFR-I and 0.04 for TNFR-II). Levels of sTNFR-I and sTNFR-II were comparable for advanced endometriosis and controls, and between early and advanced endometriosis. As a biomarker for all- stage endometriosis, sTNFR-I produces AUC of 0.62, sensitivity of 61%, and specificity of 47.3%, at a cutoff of 81.87pg/ml. For early stage disease, sTNFR-I yields AUC of 0.68, sensitivity of 60.7%, specificity of 75%, at a cutoff of 351.22pg/ml. CONCLUSION sTNFR-I is significantly higher in serum of endometriosis patients than controls. As an endometriosis biomarker, sTNFR-I achieves better performance for early stage disease.

Synthesis of New 3-Substituted-5-(2-hydroxyethyl)-3,4,5,6-tetrahydro-2H-l,3,5-thiadiazine-2-thione Derivatives with Potential Antimicrobial Activity

The purpose of this study is based upon design and synthesis of a new series of flexible molecules of 3,4,5,6‐tetrahydro‐2H‐1,3,5‐thiadiazine‐2‐thione (THTT) derivatives depending upon incorporation of 2‐aminoethanol as a part of the polar moiety in this nucleus. Thirteen derivatives of 3‐substituted‐5‐(2‐hydroxyethyl)‐3,4,5,6‐tetrahydro‐2H‐1,3,5‐thiadiazine‐2‐thione were synthesized by reaction of the appropriate alkyl, cycloalkyl, aralkyl amine, or glycine with carbon disulphide, formaldehyde, and 2‐aminoethanol. The structures of the target compounds were elucidated using spectral methods as well as elemental analyses. A mass‐spectrometry study was carried out on representatives of the synthesized derivatives. The title compounds were tested for their antibacterial activity in vitro against some gram positive and gram negative bacteria. The in‐vitro antifungal activity was tested against dermatophytic, saprophytic, phytopathogenic, and antagonistic fungi. In most cases, the newly synthesized compounds 4–16 exhibited a considerable inhibitory effect on the growth of some of the tested organisms in comparison to that of ampicillin or muconazole as reference drugs. Moreover, the results indicated that the polar hydroxyethyl group at the N5‐ and the lipophilic one at the N3‐positions are essential for the antimicrobial activity of the tested compounds.

Transvaginal Doppler sonography for evaluation of irregular uterine bleeding with DMPA

BackgroundThe main cause for discontinuation of depot medroxyprogesterone acetate (DMPA) use is irregular menstrual bleeding. The exact pathophysiological mechanisms of irregular bleeding have remained unclear. Transvaginal Doppler is a non-invasive method for studying changes in blood flow which may highlight the underlying pathology in those cases with irregular uterine bleeding. The aim of this study was to quantify the uterine and subendometrial microvasculature in DMPA users with irregular bleeding pattern in comparison to DMPA users with amenorrhea.Study designThis is a case control study. Forty users of DMPA were divided into two groups: one group included 20 users with irregular uterine bleeding and the second group included 20 amenorrheic users. Pulsatility index (PI) and resistance index (RI) of uterine and subendometrial blood vessels were determined. Power Doppler Energy was used to quantify the signal percentage of the subendometrial area.ResultsThere is significant reduction of PI and RI in the uterine artery and subendometrial microvasculature in cases of irregular uterine bleeding.ConclusionIrregular uterine bleeding with DMPA associated with increased perfusion of uterine and subendometrial blood vessels.