AIM OF THE WORK: The aim of the present study is to document the antitumor activity of the combination of gemcitabine and cisplatin for the treatment of advanced NSCLC, asses the nature and severity of the side effects and elicit the impact of the combination chemotherapy on progression free survival and overall survival.

PATIENTS AND METHODS: From August 1997 to August 2001, we conducted a phase II study of gemcitabine and cisplatin in 60 chemonaive patients (21 stage IIIB and 39 stage IV). For the first 34 cases, gemcitabine was given at a dose of 1,000 mg/m2 IV on days 1, 8 and 15 with cisplatin 100 mg/m2 on day 15, every 28 days. In the following 26 patients, the regimen was modified to gemcitabine 1,250 mg/m2 days 1 and 8 and cisplatin 80 mg/m2 day 1, every 21 days.

RESULTS: Patients included 53 males and 7 females [median age, 52 years (range, 28-69)]. Twenty-nine had adenocarcinoma, 18 large-cell carcinoma and 13 squamous-cell carcinoma. Thirty-one patients had a performance status (PS) of 2 and 22 presented with weight loss. All patients were evaluable for response. Three patients achieved a complete response (CR) and 22 had partial response (PR), giving an overall response of 41.7%, with a median duration of 10 months (range, 4-46 months). The time to progression (TTP) was 8 months (range, 2-46 months), with a median overall survival of 9 months (range, 2-46 months). The one-year survival rate was 30.3% for the entire study population, 44% for responders, and statistically improved in patients with a PS of I and those with no weight loss. A total of 255 cycles were administered (median, four cycles/patient). Myelosuppression was significant (but manageable) with grade 3/4 neutropenia in 32.6% of cases, anemia in 18.6% and thrombocytopenia in 20.4%. Nonhematologic toxicity was limited to grade 3/4 nausea and vomiting in 28.8% of cases and impaired liver enzymes in 13.6%.

CONCLUSION: Inspite of the relatively poor prognostic characteristics in the study population, gemcitabine and cisplatin, was an effective combination with tolerable, manageable toxicity in advanced NSCLC.

The effect of long-term treatment of chloroquine (CAS 54-05-7) (20 mg/kg body weight) on serum lipid components and its relation to to the retinotoxic effect was studied in albino rats. Chloroquine was found to form lamellar lysosome-like structures within the photoreceptive layer, as well as the pigment epithelium and neurooretinal layers. Biochemically, hypolipidemia in the serum was observed mainly due to the decrease in phospholipid portion. It was hypothesized that due to the inhibition of the degradation process in the defective lysosomes, the retinal cells were denied the re-use of their own phospholipids, and thereby resort to their uptake from the serum.

Pichia pinus biomass obtained from growth on methanol medium was fed to rats as 10% protein of the diet. Its nutritional, Physiological and histological effects were estimated. The protein efficiency ratio (PER) and the apparent digestibility of the biomass (Dapp) were 2.74 ± 0.107 and 73.99 ± 1.21, respectively, while that of casein (control) were 2.91 ± 0.127 and 90.16 ± 0.64, respectively. the alkaline phosphatase levels mostly showed no significant difference from the control. While the GOT levels were mostly significantly lowered, and the GPT levels did not show consistency. The urea nitrogen and creatinine levels in serum were unchanged, While that of uric acid was only significantly increased after 35 feeding days. Histologically no changes were observed.

Glucose tolerance (GT), peripheral insulin activity (A) and beta cell function (CIR) were improved on prolonged chloroquine administration to normal male rats, while the acute effects comprised hyperinsulinaemia with unaltered blood glucose levels. This study explains some of the seemingly conflicting results due to chloroquine treatment and concludes that the drug is not damaging to glucose homeostasis in long term treatment.

Seven samples of the system Cu1-x Cd x Fe 2O4 were prepared by thermal decomposition of mixed metal oxalates with x = 0.0, 0.1, 0.3, 0.5, 0.7, 0.9 and 1.0. The formation of the ferrispinel was studied by XRD, FT-IR, Mössbauer spectroscopy, electrical conductivity and magnetic susceptibility measurements. XRD showed single cubic spinel phase for all the samples except for CuFe2O4 sample which shows a tetragonal structure. An increase in the lattice parameter of the ferrispinel was observed with increasing the cadmium content. The temperature variation of ac conductivity showed four definite regions with three transitions which attribute to the change in the conduction mechanism with increasing temperature. Magnetic properties of the sample with x ≤ 0.5 showed a decrease in the effective magnetic moment with the increase in the cadmium content which means that the ferromagnetics are widely separated and enclosed by non-magnetic cadmium ions. A well defined hyperfine Zeeman spectrum is observed for samples with x ≥ 0.3 at room temperature and resolved into two sextets corresponding to the octahedral and tetrahedral sites. The propable ionic configuration of the system proposed is (Cd x Cu y Fe1-x-y )[Cu1-x-y Fe1+x+y ]O4. © 2005 Springer Science + Business Media, Inc.

Seven samples of the system Cu1-x Cd x Fe 2O4 were prepared by thermal decomposition of mixed metal oxalates with x = 0.0, 0.1, 0.3, 0.5, 0.7, 0.9 and 1.0. The formation of the ferrispinel was studied by XRD, FT-IR, Mössbauer spectroscopy, electrical conductivity and magnetic susceptibility measurements. XRD showed single cubic spinel phase for all the samples except for CuFe2O4 sample which shows a tetragonal structure. An increase in the lattice parameter of the ferrispinel was observed with increasing the cadmium content. The temperature variation of ac conductivity showed four definite regions with three transitions which attribute to the change in the conduction mechanism with increasing temperature. Magnetic properties of the sample with x ≤ 0.5 showed a decrease in the effective magnetic moment with the increase in the cadmium content which means that the ferromagnetics are widely separated and enclosed by non-magnetic cadmium ions. A well defined hyperfine Zeeman spectrum is observed for samples with x ≥ 0.3 at room temperature and resolved into two sextets corresponding to the octahedral and tetrahedral sites. The propable ionic configuration of the system proposed is (Cd x Cu y Fe1-x-y )[Cu1-x-y Fe1+x+y ]O4. © 2005 Springer Science + Business Media, Inc.

Endometrial stromal sarcoma (ESS) is a rare neoplasm of uterine origin. Intracardiac metastasis from this tumor is extremely infrequent. This report describes a 24-year-old woman from Yemen who had irregular vaginal bleeding shortly after spontaneous abortion. She developed left-lower-limb swelling, diagnosed by duplex scanning and magnetic resonance imaging as deep venous thrombosis in the inferior vena cava (IVC) that extended into the iliac veins on both sides, as well as the left femoral vein and right atrium. She developed acute respiratory distress, from which she recovered after transfer to the intensive care unit. Transesophageal echocardiography showed a large mass occupying the right atrium and ventricle and another mass in the right ventricular outflow tract with areas of cavitations. The tumor appeared to come from the IVC and extended through the right atrium and right ventricle into the pulmonary artery, ending in several digit-like projections. After surgical resection of the intracardiac mass, pathologic examination revealed a low-grade ESS that was confirmed by immunohistochemistry. The patient underwent panhysterectomy and IVC debridement. Pathologic examination revealed infiltrating low-grade endometrial sarcoma invading the myometrium and left adnexa, with intravenous extension into the pelvic veins and the IVC to the right side of the heart. This case shows that despite its well-known good prognostic nature, low-grade ESS may behave as an aggressive malignancy.

Seven samples of the system Cu1-x Cd x Fe 2O4 were prepared by thermal decomposition of mixed metal oxalates with x = 0.0, 0.1, 0.3, 0.5, 0.7, 0.9 and 1.0. The formation of the ferrispinel was studied by XRD, FT-IR, Mössbauer spectroscopy, electrical conductivity and magnetic susceptibility measurements. XRD showed single cubic spinel phase for all the samples except for CuFe2O4 sample which shows a tetragonal structure. An increase in the lattice parameter of the ferrispinel was observed with increasing the cadmium content. The temperature variation of ac conductivity showed four definite regions with three transitions which attribute to the change in the conduction mechanism with increasing temperature. Magnetic properties of the sample with x ≤ 0.5 showed a decrease in the effective magnetic moment with the increase in the cadmium content which means that the ferromagnetics are widely separated and enclosed by non-magnetic cadmium ions. A well defined hyperfine Zeeman spectrum is observed for samples with x ≥ 0.3 at room temperature and resolved into two sextets corresponding to the octahedral and tetrahedral sites. The propable ionic configuration of the system proposed is (Cd x Cu y Fe1-x-y )[Cu1-x-y Fe1+x+y ]O4. © 2005 Springer Science + Business Media, Inc.

The aim of this study was to investigate the influence of the nanocarrier surface charge on brain delivery of a model hydrophilic drug via the nasal route. Anionic and cationic nanostructured lipid carriers (NLCs) were prepared and optimized for their particle size and zeta potential. The optimum particles were incorporated in poloxamer in situ gels and their in vivo behavior was studied in the plasma and brain after administration to rats. Optimum anionic and cationic NLCs of size <200 nm and absolute zeta potential value of ≈34 mV were obtained. Toxicity study revealed mild to moderate reversible inflammation of the nasal epithelium in rats treated with the anionic NLCs (A7), and destruction of the lining mucosal nasal epithelium in rats treated with the cationic NLCs (C7L). The absolute bioavailability of both drug loaded anionic and cationic NLCs in situ gels was enhanced compared to that of the intranasal solution (IN) of the drug with values of 44% and 77.3%, respectively. Cationic NLCs in situ gel showed a non significant higher Cmax (maximum concentration) in the brain compared to the anionic NLCs in situ gel. Anionic NLCs in situ gel gave highest drug targeting efficiency in the brain (DTE%) with a value of 158.5 which is nearly 1.2 times that of the cationic NLCs in situ gel. © 2014 Elsevier B.V.

The role of estrogen and its receptors in the etiology and progression of prostate cancer ( PC ) is poorly understood. In normal and malignant human prostate, estrogen receptor-a is expressed only in the stroma, whereas estrogen receptor-Beta ( ER-Beta ) is present in both normal stroma and epithelium. Because loss of ER-Beta expression is associated with prostate hyperplasia in ER-Beta null mice, this study determined patterns of ERBeta expression in hyperplastic, PIN ( prostatic intraepithelial neoplasia ) and malignant human prostate and associations with tumor progression. Formalin-fixed, paraffin-embedded blocks were obtained from thirty-five patients who underwent radical prostatectomy and pelvic lymphadenectomy for prostate cancer, 15 core biopsies diagnosed as PIN and 10 TURP ( transurethral prostatic resection ) diagnosed as BPH ( benign prostatic hyperplasia ) were assessed for ER-Beta expression using immunohistochemistry. ER-Beta positivity was defined as 5% of cells demonstrating nuclear immunoreactivity. Nine ( 90% ) of the studied BPH cases showed ER-Beta positive expression where they showed 5% ER-Beta positive cells, while eight ( 53% ) of the studied 15 PIN cases were negative for ER-Beta expression. Twenty-nine ( 82.8% ) of the studied adenocarcinoma cases were negative for ERBeta expression, p<0 .0001. The loss of ER-Beta expression is associated with progression from hyperplastic prostate epithelium to PC. The ER-Beta expression is inversely proportional to PCs stage and grade. From these data we can conclude that estrogen can affect prostatic cancerogenesis and neoplastic progression through an ER-Beta mediated process in human prostate tissue. Our data also identify the need for additional studies to address the potential role of ERBeta in the regulation of prostate epithelial cell proliferation at different stages in the development of PC. Key Words:ER Beta - Prostatic hyperplasia - PIN - Prostatic carcinoma.