Pulsatile Chronotherapeutic Drug Delivery for Controlling Early Morning Surge in Blood Pressure; Effect of Coating on Eplerenone In-vitro, In-vivo Release and Urinary Na/K Ratio

Abstract The objective of the present study was to develop time delayed chronotherapeutic formulation of Eplerenone (Ep) to provide rapid drug release after a pre-determined lag time for the treatment of early morning hypertension. Cyclodextrin complexation was used to prepare fast release Ep core tablets. The developed core tablets were then coated with different rate-controlling polymers using compression coating technique. The developed tablets were evaluated for hardness, friability, drug content and swelling index. The in-vitro drug release was carried out to study the effect of different coating materials on drug release and lag time. Tablets selected for stability study were those showing lag time of 5-7 hours followed by complete drug release; F2, F3, F7, F8, and F12. The in-vivo study was carried out on tablets with the highest t90 as compared to commercial tablets after being administered to healthy human volunteers where plasma Ep and urinary Na/K ratio were determined. Results suggested that this approach was able to provide delayed release Ep formulations that will be useful for patients with morning surge in blood pressure.

Verapamil as an adjunct to local anaesthetic for brachial plexus blocks

Background: Upper extremity surgeries are recently performed under regional anesthesia. Regional anesthesia of the upper extremity has several advantages over general anesthesia, such as improved postoperative pain, decreased postoperative narcotic consumption, and reduced recovery time. Supraclavicular approach of the brachial plexus block has gained importance for surgical and interventional pain management purposes. Supraclavicular brachial plexus block provides an ideal condition for surgery of the upper limb, maintains hemodynamic stability, decreases postoperative pain and allows for early ambulation. However, the duration of the supraclavicular brachial plexus block is limited by the duration of action of the local anesthetic used in the block

Aim of the Work: The aim of this study is to evaluate whether additional anesthetic effects could be derived from addition of verapamil into local anesthetics injected into brachial plexus sheath

Patients and Methods: This study was a prospective, randomized, controlled, double blind study had been carried out in Matareya Teaching Hospital on 60 adult patients with a physical status ASA I and II classification scheduled for upper limb surgeries for 6 months. Patients were randomly classified using sealed envelopes into two equal groups [group I and group II] each of 30 patients. Group I: 30 patients who received 40 ml of 1% lignocaine [20ml] with 0.25% bupivacaine solution [20ml], Group II: 30 patients who received 40 ml of 1% lignocaine[20ml] with 0.25% bupivacaine solution with 2.5mg verapamil [20ml]

Results: Onset of sensory blockade time was marginally faster in Group II [12 +/-1.8minutes] as compared to Group I [12.6 +/- 1.4 minutes]. However this difference was statistically not significant. The increase in duration of sensory blockade in Group II [209.90 +/- 13.22 minutes] as compared to Group I [183.80 +/- 11.68 minutes] was statistically significant [p < 0.001]. Increase in duration of motor blockade in Group II [172.00 +/- 9.32 minutes] as compared to Group I [168.20 +/- 8.91 minutes] was statistically not significant [p = 0.112]

Conclusion: we conclude that adding 2.5 mg verapamil with 0.25% bupivacaine solution [20ml] with 1% lignocaine [20ml] to brachial plexus block can prolong sensory anesthesia without significant effect on duration of motor block, onset of sensory and motor block

Assessment of the role of paraoxonase gene polymorphism [Q192R] and paraoxonase activity in the susceptibility to atherosclerosis among lead-exposed workers

Lead exposure is a well known cause of cardiovascular damage, including atherosclerosis. Paraoxonase 1 [PON1], a high-density lipoprotein-associated antioxidant enzyme, is capable of hydrolyzing oxidized lipids and thus it protects against atherosclerosis. The mechanism by which heavy metals inhibit serum PON1 activity is still not clear. Our aim was to detect the association between lead exposure and serum PON1 activity and lipid profile and also to study the polymorphism of the PON1 gene. A case-control, cross-sectional study conducted from June 2008 until May 2009. Male workers [n=100] in a lead battery manufactory were recruited for this study. They were compared with 100 male age-matched workers not exposed to lead [control group]. Serum lipid profile, paraoxonase activity and lead were measured in blood samples. The DMA was extracted for detecting the Q192R polymorphism of the PON1 gene by polymerase chain reaction followed by restriction fragment length polymorphism. There was significant difference in triglycerides, total cholesterol and high-density lipoprotein cholesterol [HDL-C] [P=.01,.05 and.04, respectively] between cases and controls. Multiple linear regression analysis showed that blood lead levels were significantly associated with decreased serum paraoxonase activity [P=.03] in lead workers. The paraoxonase genotype QR was the most prevalent in 34/53 subjects [64%] among the leadexposed groups, while the genotype QQ was more prevalent in the control group, in 1 5/25 subjects [60%], with a significant difference between the control and other groups [P<.05]. Lead exposure is associated with increased triglycerides, total cholesterol and low-density lipoprotein cholesterol and decreased HDL-C. Because of the protective role of PON1 in the development of atherosclerosis, a decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis

BRCA1 gene expression in women breast cancer in relation to other prognostic markers

Breast cancer causes major part of cancer deaths in women and is increasing in incidence. This study assessed the BRCA1 gene expression in breast cancer in women, and compared it with other known prognostic factors for the disease. Thirty patients with positive family history of breast cancer were selected from Beni-Suef and Cairo Universities Hospitals, Egypt for the study. A control group of 10 healthy subjects were also included. Blood samples were withdrawn for routine laboratory and tumor marker [CA15-3] being done by ADVIA Centaur. Archival formalin-fixed paraffin-embedded breast cancer tissues were obtained from the pathology files. Histological types and grading of the tumor were assayed. The immunohistochemistry [IHC] and RNA extraction were also done. Histological grading of the carcinomas was done according to the system of Scarff-Bloom-Richardson. Cells from MCF-7 cell line grown in Roswell medium [Gibco BRL] and known to express BRCA1 were processed into paraffin and used as positive controls for both IHC and real-time reverse transcription-polymerase chain reaction [RT-PCR]. BRCA1 expression was correlated with age, histological type and grade of breast cancer, estrogen and progesterone receptor status, and CA15-3. After statistical analysis of the data, demonstrable BRCA1 mRNA was found in 6 patients samples [20% of the breast cancer tissues] while the other patients showed 80% negative BRCA1 mRNA expression as well as the control group. A positive significant relationship was demonstrated between BRCA1 [mRNA] expression and high histological grade, negative estrogen and progesterone receptor status, and high levels of serum CA15-3. A significant negative correlation was found between BRCA1 mRNA expression and age [r=-0.683; p<0.01] The study demonstrated lack of BRCA 1 gene expression [mRNA] in the majority of breast cancers in Egypt and confirmed the relationship between BRCA1 expression and parameters that determine poor prognosis in breast cancer. Our results suggested that BRCA1 is seen in high-risk women known with positive family history of breast cancer. Strategies for recruitment of Egyptian women in studies of genetic testing for different breast cancer genes have varied levels of success. Our study highlights the need for further studies in this population group

Altered serum lipids and paraoxonase activity: a step toward at herosclerosis among lead exposed Egyptian workers

A vast amount of evidence during the past decade, has confirmed that lead is associated with lipid and lipoprotein abnormalities which play a major role in the pathogenesis and progression of atherosclerosis and cardiovascular diseases. This study aimed: to investigate the relationship between chronic occupational lead exposure, lipid profile, and serum PON1 activity as one of the mechanisms of atherosclerosis. Male workers [n=100] in lead battery manufactory were recruited for this study. They were compared with 100 male age matched non-lead workers. Serum lipid profile and paraoxonase activity were done to their samples. Serum Lead was determined vsing atomic absorption spectroscopy. There was significant differences regarding triglycerides, total cholesterol, and HDL- c [p=0.01, 0.05 and 0.04, respectively] between both groups. A cumulative effect of blood lead on lipid profile was significantly detected. Multiple linear regression analysis showed that blood lead level was the only negative significant predictors to serum paraoxonase activity [p=0.03] in lead workers. lead exposure is associated with increased triglycerides, total cholesterol and LDL-c and decrease HDL-c. Because of the protective role of PON1 in the development of atherosclerosis, decrease in serum PON1 activity due to lead exposure may render individuals more susceptible to atherosclerosis

Amplification of human telomerase reverse transcriptase gene as a diagnostic marker in lung cancer

Analysis of circulating DNA or RNA in plasma can provide a useful marker for earlier lung cancer detection. This study was designed to assess the sensitivity and specificity of a quantitative molecular assay of circulating RNA to identify patients with lung cancer with different grades. The amount of plasma RNA was determined through the use of real-time quantitative polymerase chain reaction [PCR] amplification of the human telomerase reverse transcriptase gene [hTERT] in 19 non-small-cell lung cancer patients and 10 age and sex matched controls. Performance of the assay was calculated through the receiver operating characteristic [ROC] curve. The hTERT mRNA ratio in cancer lung patients showed a mean of 196.34 +/- 307.23 which was higher compared to that of the controls 1.24 +/- 0.80; this difference was statistically highly significant where P<0.01. The median concentration of circulating plasma RNA in patients was higher than the value detected in controls [71.70 v 1.149 ratio]. Plasma RNA was a strong risk factor for lung cancer; concentrations in the patients were associated with a 62-fold higher risk than were those in the controls. The point of the best cut-off value was at 2.24 where sensitivity was 73.7% and specificity was 90%. The area under the ROC curve was 0.704. This study shows that higher levels of free circulating RNA can be detected in patients with lung cancer compared with disease-free heavy smokers by a PCR assay, and suggests a new, noninvasive approach for early detection of lung cancer. Levels of plasma RNA is recommended to be measured as it could also identify higher-risk individuals for lung cancer screening and chemoprevention trials

Relaibility of salivary testosterone measurements in diagnosis of polycystic ovarian syndrome

The aim of this study was to evaluate the reliability of a non-invasive method [saliva] for determination or testosterone level in diagnosing cases of Polycystic Ovarian Syndrome [PCOS], and comparing it with serum free testosterone. Fifty women with PCOS and 20 normal women as control group were selected for the study. They all aged between 23-35 years. For all patients serum follicle stimulating hormone [FSH] and lutinizing hormone [LH] were assessed by chemiluminscent assay. Serum free testosterone [FT] was assayed by Radioimmunoassay [RIA] and salivary testosterone [ST] by ELISA technique. BMI was calculated for all participants and transvaginal sonography to determine ovarian morophology and ovarian volume. The present study showed a significant positive correlation between salivary testosterone, as measured by ELISA, and serum free testosterone measured by RIA [P=0.001 and r=0.52]. Using the receiver operator curve, salivary testosterone was found to be more sensitive than serum [FT] [84% VS 66%] in diagnosing PCOS patients. Determination of salivary testosterone is a reliable method to detect changes in the concentration of available biologically active testosterone in the serum. Salivary testosterone provides a sensitive, simple, reliable, non-invasive and uncomplicated diagnostic approach for PCOS

Evaluation of some biochemical markers of cancer prostate

The incidence of Cancer Prostate [PCa] has increased dramatically during the last 10-15 years many strategies have been proposed to enhance the ability of PSA in differentiation of PCa from BPH and f/t PSA was one of those strategies that were reported to improve the diagnostic accuracy of PSA. Of these markers we evaluated prostatic specific antigen [PSA], Neurone specific enolase [NSE], Tissue polypeptide specific antigen [TPS] and Scatter factor [SF], also known as hepatocyte growth factor [HGF]. The present study aimed at evaluating the measurement of serum levels of NSE, TPS and HGF in combination with PSA and I7t PSA in cancer prostate patients to assess their diagnostic and prognostic value in such patients. The study was conducted on 72 patients complaining of obstructive symptoms as frequency and urgency. The first group comprised 26 subjects diagnosed as BPH, the second group consisted of 21 subjects diagnosed as localized PCa and the third group consisted of 25 subjects diagnosed as metastatic PCa. The latter group was further divided according to Gleason score into moderately differentiated [n=13] and poorly differentiated adenocarcinoma [n=12]. All patients were subjected to transrectal ultrasonography [TRUS] and core needle biopsy from the prostate for histopathological examination, and assay of serum tPSA, fPSA measured by chemiluminescent immunometric assay, NSE using electrochemiluminescence immunometric assay, TPS [1RMA] and HGF [ELISA]. Median values of tPSA was significantly higher in metastatic PCa [group III] compared to localized PCa [group II] and BPH patients [group I] [68, 7.0, 2.0ng/ml respectively P<0.001], f/t PSA was significantly lower in PCa patients [group II, group III] compared to BPH patients [0.13, 0.14,0.2 respectively, P=0.004], TPS was significantly higher in metastatic PCa [140U/L] compared to group I and group II [77,65U/L, respectively P=0.004] and HGF was significantly highest in metastatic PCa patients compared to group I and group II [2270, 2132, 1789pg/ml, respectively, P=0.047]. A statistical significant positive correlation was found in the malignant group between PSA and HGF and between [TPS] on one hand and [NSE and HGF] on the other hand. Simultaneous assay of PSA and HGF yielded a sensitivity of 96% in discriminating between BPH from malignant prostate compared to 91% for HGF and 93% for PSA alone. Higher NSE levels were found in higher stage and higher grade PCa. On evaluating the metastatic PCa group, it was found that poor PSA progression free survival [shorter time to androgen responsiveness] is associated with high NSE levels, and with poorly differentiated adenocarcinoma [high Gleason score 8-10]. The value of tPSA in diagnosing cancer prostate is still of uncertainty, however, it is better to be combined with f/tPSA assay. The f/tPSA is useful in discriminating between BPH and PCa especially in the early stage [localized PCa] and thus allowing early intervention and treatment. A cutoff value of 0.24 for f/tPSA is recommended as it detects 87% of cancer cases and at the same time avoids 39% of unnecessary prostate biopsy. Moreover, combining PSA and HGF was more accurate in discriminating between BPH and malignant prostate than either marker alone. HGF alone is of prognostic significance especially in the presence of metastates and correlates well with the stage and grade of cancer prostate. An increase in TPS signifies clinical progression even if PSA is found to remain normal. Thus it is of value in overcoming the relative insensitivity of PSA in some of hormonally treated patients. High NSE levels are of prognostic significance in patients with metastatic PCa treated with androgen withdrawal therapy

Subclinical hyperthyroidism as a potential factor for dysfunctional uterine bleeding

To evaluate the functional status of thyroid gland in apparently euthyroid women with dysfunctional uterine bleeding. Forty apparently euthyroid women with menorrhagia and no pathologic lesion in the genital tract were compared to 20 women having normal menstrual cycle as control group. All women were subjected to hormonal assay: total and free T3, T4 and TSH, Serum PRL, P [progesterone], total and free testosterone. A statistically significant difference in the values of TSH, total T3, free T3 and total T4 in the menorrhagia group compared to the control group. Prolactin was decreased significantly in the menorrhagia group. Subclinical hyperthyroidism can be a potential risk factor for dysfunctional uterine bleeding. Other studies are needed to confirm our findings

Cervicovaginal fibronectin as a predictive marker for success of induction of labor in prolonged pregnancy compared with the traditionally used bishop score

To compare cervical fibronectin as predictive marker for success of induction of labor compared with the traditionally was Bishop Score. Setting: Kasr EL-Aini Hospital. Design: A prospective controlled trial. Participants and 100 fullterm singleton pregnant women undergoing labor induction due to postdatism were examined to determine Bischop score and cervicovaginal fibronectin was assessed using fast reacting membrane immunoassay. There was a highly significant difference in the success of labor induction between women with positive and negative fibronectin test results. P<0.001. Fibronectin compared to Bishop Score has Sensitivity of 64.5%, Specificity of 44.8%, Positive predictive value of 78.9%, Negative predictive value of 54.2%, accuracy = 73%. Fetal fibronectin is a simple, easy and sensitive test for prediction of successful labor induction in women with prolonged pregnancy. If fetal fibronectin test in negative, induction of labor should be considered in women only with high Bishop Score.

Interleukin-8 compared to fetal fibronectin for prediction of preterm labor in women with twin pregnancy: a prospective cross sectional study

To investigate the value of measuring IL-8 compared to Fetal Fibronectin [FFN] for predicting preterm labor in twin pregnancy. Prospective controlled trial. Thirty twin pregnant women between 28-34 weeks gestation not in labor were compared to thirty twin pregnancy women having preterm labor. Cervicovaginal fluid was collected from all cases for detection of Fetal fibronectin and Interleukin-8. IL-8 level at a cut off value of 1500pg/ml had a sensitivity 93.3%, a specificity 96.7%, a positive predictive value 96.6% and a negative predictive value 93.3%. These Figures were better than FFN level which had a sensitivity 90.0%, a specificity 86.7%, a positive predictive value 87.1% and a negative predictive value 89.7% in diagnosis of patients with premature labor. In twin pregnancies a biochemical markers such as fetal fibronectin and interleukin-8 could be considered a useful tool in clinical practice for early identification of women at risk of preterm labor

Evaluating the value of sonographic criteria for polycystic ovary compared to endocrine profile

To evaluate the reliability of using transvaginal sonography criteria and Doppler examination for diagnosis of polycystic ovarian disease compared to hormonal profile of these cases. prospective controlled trial. Kasr El-Aini Hospital. Participants and Seventy eight women were enrolled in the present study. Forty eight of them were infertile women shown to have elevated LH/FSH ratio [Group I]. Group II included 30 apparently normal parous women nonhirsute, non obese, with normal menstrual rhythm. Detailed assessment of the ovary for all cases was done using transvaginal ultrasonogmphy and Doppler examination and the following was recorded: ovarian volume, stromal width, number of follicles, and peak stromal blood flow velocity. The mean ovarian volume in the study group [13.4] was significantly higher than mean ovarian ' volume in the control group [7.8] [P <0.05]. The mean number of follicles in the study group [11.2] was significantly higher than that of the control group [4.3] [P <0.05]. The mean stromal width in the study group [16.3mm] was also significantly higher than that of the control group [8.8mm] [P <0.05]. Peak stromnl blood flow velocity also showed significant difference between both groups [9.6 vs 6,6 [cm/s]]. Increased stromal width showed the highest sensitivity amongst all the ultrasonographic morphological criteria. Transvaginal ultrasonography is a valuable tool for diagnosis of FCO. Stromal width as a single test appears to be the most favorable screening test to predict endocrine abnormalities characteristic for PCOS