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Background: The mortality from coronary heart disease (CHD) has been steadily increasing in many parts of the world. Measures to reduce the incidence of CHD were initially addressed mainly to middle aged and elderly population groups, but for effective prevention of CHD, measures addressed to younger age groups are also necessary. Moreover, differences between male and female plasma lipid changes after exercise training are not known exactly., Methods: The concentrations of plasma lipids, before and after regular physical exercise training for 12 weeks, were analyzed in 25 male and 25 female medical students of the same age group. Physical fitness was evaluated by the measurement of maximum oxygen uptake., Results: Results indicated that plasma tri-glyceride, HDL-cholesterol, LDL-cholesterol and VLDL-cholesterol differences between the before-and-after exercise were significant (p < 0.05) in males while the differences of plasma total cholesterol were found to be insignificant. In females there were no significant changes in the plasma lipids levels. In both males and females, the marked increase in maximal O2 uptake after exercise training indicated an improvement in physical fitness., Conclusions: This study concludes that a short-term exercise program can improve plasma lipid and lipoprotein patterns more in males than in females. It also suggests that daily physical exercise may be an important prevention for cardiovascular diseases in later life, so it is essential to establish a life style with optimum nutrition and physical activity in both the young and in adults of all ages.

Background: Despite some findings to the contrary, it would appear that pharmacological doses of progesterone and estrogen (alone or in combination) can influence intraocular pressure (IOP). The relationship between hormonal changes associated with the menstrual cycle and intraocular pressure is not clearly understood. After elimination of those factors that can affect IOP, the present study investigated whether physiological hormonal changes associated with the menstrual cycle have a correlation with intraocular pressure., Methods: Intraocular pressure and the concentrations of circulating hormones, namely, the luteinizing hormone (LH), follicle-stimulating hormone (FSH), estrone (E1), estradiol (E2), progesterone, and testosterone, of twenty married women of the same age groups were recorded daily throughout a menstrual cycle. None was taking any contraceptives in any form. The intraocular pressure was measured using a Goldmann applanation tonometer., Results: The intraocular pressure values fluctuated in each of the twenty subjects at various times of the cycle; however, they were not definitely correlated with the different phases of the cycle. This study failed to find any correlation between IOP and progesterone or estradiol levels.

Intraocular pressure (IOP) has never been compared between hard working and sedentary subjects. The relationship between physical fitness and IOP is not clearly known. There are only two studies and their results are contradictory. The variability in their results may be due to several factors. Therefore, the present study was planned to investigate the relationship between working style, physical fitness and IOP after taking into account those factors that can affect IOP. One hundred fifty male volunteers of a steel factory were divided equally in two groups. The subjects of group 1 were sedentary worker, whereas group 2 subjects were actively engaged in heavy works requiring exertion. Physical fitness was evaluated by the measurement of maximum oxygen uptake with a Bechman O2 analyzer. IOP was measured with the Goldmann applanation tonometer. As compared to sedentary subjects, maximum oxygen uptake was significantly higher whereas IOP was significantly lower in those who did moderate or severe exertions. The maximum oxygen uptake difference between group 1 and 2 was found to be (mean +/- SD) 5.1 +/- 1.1 ml/kg/min (p < 0.001), whereas, IOP difference was 1.9 +/- 0.7 mmHg (p < 0.001). This study concludes that hard working is associated with physical fitness and physical fitness is associated with reduced resting IOP. It would seem reasonable at present not to discourage subjects who have ocular hypertension from exercise; perhaps, on the contrary, it should be encouraged to increase their physical fitness.

Transdermal patches were developed and evaluated for two synthetic derivatives of capsaicin, nonivamide (NVA) and sodium nonivamide acetate (SNA), by in vitro and in vivo skin permeation. The designed system was essentially based on natural rubber or polymeric Gelva dispersion. The characterization of physicochemical properties of the patches showed adequate adhesive force and low thickness which suggested these patch formulations possessed good quality. In the study of in vitro percutaneous experiment, the predicted therapeutic activities of patches were all higher than that of a commercially available plaster after the calculation of antinociceptive index. The highest in vitro penetration flux was found in the Gelva patch for NVA. The result of in vivo experiments revealed a high obverse correlation with that of in vitro experiments. The information of this present study is helpful for the further development of NVA and SNA transdermal drug delivery system.

The present study was planned to investigate the relationship between the magnitude of intraocular pressure (IOP) reduction after short-duration exercise and the intensity, duration and quantity of exercise in healthy subjects. Twenty-five healthy, sedentary male of the same age group, performed exercises at the levels of 80%, 60%, and 40% maximum heart rate (HRmax) for 15 minutes, 80% HRmax for 7.5 minutes, 60% HRmax for 10 minutes, and 40% HRmax for 30 minutes. IOP was measured with the Goldmann applanation tonometer. The IOP reduction at 5 minutes after 15 minutes of exercising at 80% HRmax, 60% HRmax, and 40% HRmax were 4.7 +/- 0.9, 3.5 +/- 0.7, and 0.9 +/- 0.4 mmHg, respectively. At five minutes, after exercising 7.5 minutes at 80% HRmax, 10 minutes at 60% HRmax, and 30 minutes at 40% HRmax, IOP reduced by 4.5 +/- 0.7, 3.3 +/- 0.9, and 2.9 +/- 1.1 mmHg, respectively. This study concludes that intensity of exercise seems responsible for the magnitude of the initial IOP decrease after short-term exercise. Furthermore, it seems that other factors such as duration of exercise or quantity of exercise, blood pressures, body mass index are not related to the amount of the initial fall in IOP.

This study evaluated the distribution of Intraocular pressure (IOP) levels in 67 normal and 59 ocular hypertensive (OHT) subjects during the day after placing control on all those factors that can affect IOP. The IOP was measured with the Goldmann applanation tonometer. All the subjects were examined according to standard protocols. Both in the normal and OHT subjects, the peak of mean IOP appeared in the morning when the subjects woke up and the trough of mean IOP occurred between 2 a.m. to 4 a.m. The mean diurnal variation were (mean +/- sem) 2.9 +/- 0.7 and 3.5 +/- 0.7 mmHg in the normal and in OHT subjects, respectively. Ninety-four percent of the normal subjects and sixty-eight percent of the OHT subjects exhibited a similar diurnal behaviour in both eyes. The IOP variation did not correlate with the variations of blood pressure. The diurnal variation of IOP, found in Chinese, is lower than in other nations. The clinical importance of findings that the peaks of IOP occur in the early morning, raised a serious question as to the necessity of extending the diurnal IOP curves beyond the usual working time (JPMA 46:171, 1996).

Studies have been shown that intraocular pressure (IOP) shows a seasonal variation, but amount of change differs from study to study. The variability in their results may be due to negligence of factors that can affect IOP. Due to differences in environmental conditions of China than other countries, we investigated seasonal variations in IOP of 103 healthy male Chinese of Shanghai. IOP was measured each month over the course of fourteen months with the Goldmann applanation tonometer. The average intraocular pressures in the winter months were higher than those in the spring, summer, and autumn months. The IOP difference between winter and summer months was found to be 1.4 +/- 0.7 mmHg. This study confirms that season influences IOP. As compared to other nations, effect of seasons on IOP seems to be somewhat less pronounced in Chinese. The possible mechanisms, responsible for the seasonal variation of intraocular pressure, are also postulated.

Because the course of glaucoma is often an insidious one and most cases remain asymptomatic until the visual field has been clearly diminished, the frequency distribution of intraocular pressure (IOP) is important from both an academic and clinical viewpoint. However, diagnostically, glaucoma is a disease suited to a preventive approach. Due to differences in intrinsic constitution, diet and environmental conditions, there is a clear need for well collected population-based IOP data in different countries. In the present study, after controlling for the factors that can effect IOP, we investigated the distribution of intraocular pressure in 7201 healthy subjects of both sexes of Karachi, Pakistan. In both sexes, distribution of IOP slightly skewed towards the higher values. In males and females, 85.1% and 82.2% individuals ranged from 11 to 18 mmHg, 4.3% and 3.2% ranged from 8 to 10 mmHg, 7.1% and 11.2% ranged from 19 to 21 mmHg, respectively. Ocular hypertension (IOP > 21 mmHg) was found in 3.5% males and 3.7% females. Intraocular pressure increased with age in both eyes of both sexes. The averages per decade increase were 0.3 mmHg and 0.5 mmHg in male and female respectively. This study reports that an average per decade increase, women have 0.4 mmHg higher IOP than men. The male-female difference was not statistically significant until the age groups reached 31-40 years, after which the differences became significant. Right and left eyes IOPs were found to be 14.3 +/- 0.17 and 14.4 +/- 0.12 mmHg in male and 14.6 +/- 0.14 and 14.8 +/- 0.15 mmHg in females respectively. This survey shows that mean IOP of Pakistani population is similar to the IOP found in other epidemiologic investigations; the prevalence of ocular hypertension, however, seems to be slightly higher. Knowledge of the normal level of IOP in various age groups of both sexes will help to screen glaucoma.

Sodium nonivamide acetate (SNA) is a newly synthetic analogue of capsaicin which produces no overt pungent sensation or irritation. In this present study, the effects and roles of penetration enhancers for SNA through rat skin were investigated by in vitro skin penetration experiment and differential scanning calorimeter (DSC) determination. The penetration fluxes of SNA after the incorporation of enhancers increased in the order of Polysorbate 20 < sodium laurylsulfate < or = benzalkonium chloride. This result was consistent with that of DSC profiles which indicated the disruptive effects of surfactants on the rat stratum corneum increased in the order of Polysorbate 20 < sodium laurylsulfate < benzalkonium chloride. The information gained is particularly helpful in the development of SNA transdermal drug delivery system.

To improve drug permeation through skin, extracts of crude drugs were evaluated using in vitro and in vivo penetration techniques with rabbit skin as a model membrane. The acetone extract of Amomum cardamomum (ae-AC) and Elettaria cardamomum (ae-EC) had the best effect in enhancing the penetration of Indomethacin (IDM). The flux of IDM for the formulation containing ae-AC from pH 7.4 buffer-alcohol donor solution was 3.6 times higher than that from the 50% alcohol donor solution. In order to confirm enhancer/skin interaction, a microscopic study was carried out in order to determine the presence of physical evidence in the skin caused by enhancers. A pharmacokinetic model of percutaneous absorption of IDM after topical administration was employed on the assumption of a zero-order penetration rate through the stratum corneum followed by absorption into the blood by a first-order process. Good correlation was observed between the experimental data point and simulated plasma concentration. From the results of the study, the in vitro permeability coefficient correlates with the in vivo penetration rate through the stratum corneum.

Two commercial slow-release potassium chloride tablets, Slow-K and Addi-K have the characteristics of slow-release in the different dissolution conditions. The two tablets had similar dissolution profiles in simulated intestinal fluid (pH 6.8), simulated gastric fluid (pH 1.2) and water; which indicates that, the dissolution rates of the two commercial potassium chloride tablets are independent of the pH values of the dissolution medium. The release patterns of potassium chloride fitted the First order model and Higuchi matrix model. These were distinguished by differential rate treatment, which showed that the release followed the First order pattern. It was found that the dissolution rate of Addi-K were more rapid than Slow-K in different dissolution conditions.

Rhodostomin is a platelet aggregation inhibitor secreted by the venom gland of Calloselasma rhodostoma. We report here the isolation of a 1.67-kilobase (kb) lambda gt11 cDNA clone using degenerate oligonucleotide probe based on a partial amino acid sequence of rhodostomin. The amino acid sequence deduced from an open reading frame of the cDNA indicates that (i) the 68-amino acid sequence of rhodostomin is located at the carboxyl terminus of the precursor polypeptide and (ii) a peroxisomal targeting sequence (ser.his.ala.) exists between the stop codon and the rhodostomin sequence of the precursor. Since the amino-terminal segment of the deduced sequence shows a high degree of identity with hemorrhagic proteins, which are zinc-metalloproteinases, found in the venom of some crotalid and viperid snakes, our results also predict the existence of at least one such hemorrhagic protein in the venom of Calloselasma rhodostoma. The derivation of a platelet aggregation inhibitor and a hemorrhagic protein from the same precursor protein is consistent with the fact that these proteins may be synergistic in function.

A rapid procedure has been developed for the isolation and verification of cDNA clones isolated from a cDNA library based on lambda vectors. Using information of the partial amino acid sequence of a protein, synthetic mixed-base oligonucleotides are first employed as a screening probe using the plaque hybridization procedure. The cDNA inserts of the clones obtained are then directly amplified by polymerase chain reaction (PCR) using primers flanking the cloning site of the vector. Besides being used for cloning into a plasmid vector, the amplified DNA's are also subjected to nucleotide sequence analysis using the same mixed-base oligonucleotides as sequencing primers. This approach allows sequencing through the region of the known amino acid sequence for direct verification of the authenticity of the clones obtained. This procedure has successfully been used for cloning and partial characterization of the gene coding for a platelet aggregation inhibitor.

In the conduct of multicenter clinical trials, comparisons among the clinical centers are often made with respect to such measures as incidence of diagnosis of various events, operative mortality (in the case of a surgical trial), and patient adherence of the treatment regimen. If one or two clinics seem to stand out from all the other clinics with respect to any such measures, this may indicate - among other things - differences in skill levels or possible deficiencies in understanding and following the protocol among these clinics. On the other hand, when clinics are ranked on any measure, one clinic must of necessity be first and one last; thus, it is necessary to determine whether the extreme values represent true differences from the values of the other clinics or whether they can be attributed to random variation alone. A statistical test is described for detecting clinics that are outliers - i.e., truly different from all the rest of the clinics in the trial. Critical values for this test are given for various numbers of clinics, numbers of patients enrolled per clinic, and probabilities of a patient incurring a given event under the null hypothesis of no differences among the clinics. Use of this test in detecting outlier clinics with respect to incidence of various endpoints is illustrated for the case of a large, multicenter drug trial.

In the conduct of multicenter clinical trials, comparisons among the clinical centers are often made with respect to such measures as incidence of diagnosis of various events, operative mortality, and patients adherence to the treatment regimen. Slippage and outlier tests for statistically identifying clinics that are outliers - that is, truly different from the rest of the clinics - with respect to such measures are described. Critical values obtained for these tests by computer simulation are given for various numbers of clinics, numbers of patients enrolled per clinic, and probabilities (p) of a patient incurring a given event under the null hypothesis of no differences among the clinics. Previously published critical values based on normally distributed response variables are applicable only for p close to 0.5. The slippage and outlier tests are compared with respect to statistical power. Alternative forms of the slippage test based on the angular transformation and on hypergeometric probabilities are considered.