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New prevention strategies have been advocated to control the progression of HIV/AIDS, such as preexposure prophylaxis (PrEP). The aim of this study is to evaluate the potential changes in the oral and salivary conditions of HIV-uninfected subjects using PrEP. Subjects were evaluated before beginning the medication (T0), at the first follow-up (T1), and at the second follow-up (T2). Xerostomia, presence of untreated cavitated caries, oral hygiene habits, taste, gingival and plaque index, stimulated salivary flow rate (SSFR), and salivary concentrations of calcium, glucose, urea, and total proteins were evaluated. Data obtained were analyzed using statistical tests (p0.05), except for the salivary calcium concentration, that increased at T2 compared to T1 (p=0.02). There was significant difference between taste and xerostomia at T1 (p=0.017), and the need to drink to swallow at T2 (p=0.015). There was significant correlation between the reported amount of saliva and taste (p=0.039, r=-0.378) at T1. The prolonged use of PrEP seems to be associated with reports of dry mouth and worsening of taste, possibly associated with increased salivary calcium concentration.

Among the phytonematodes Pratylenchus brachyurus, is becoming a major concern for producers due to reduction in soybean yield. Thus, there was the effect of biological nematicide and fungicide; applied to seeds (individually or associated), performance of soybean in commercial area infested with P. brachyurous. The treatments were: T1-No control; T2-Grafinat Plus (Paecilomyces sp. + Arthrobotrys sp. + Trichoderma sp.), Biological nematicide; T3-Cropstar FS; T4-Avicta Complete; T5-Standak® Top; T6-Plus Grafinat + Cropstar FC; T7-Grafinat-Plus + Avicta Complete and T8-Grafinat Plus + Top Standak®. The results obtained showed that there was no statistical difference between treatments in plant stand, height (cm) of plants at 20, 40 and 60 days after emergence, the stem diameter (mm), the number of pods and seeds per plant, the weight of 1000 grains (g) and density. However, the application of Standak Top® (individually) and Complete Avicta in association with Grafinat Plus increased height (cm) of first pod in the plant, facilitating at harvest by reducing the grain loss. But, the greatest productivity gains (bags ha-¹) were obtained by applying Standak ® Top and Full Avicta (applied individually).

Over the past few years, a huge number of distributed camera calibration strategies have been proposed for video surveillance and monitoring systems involving mobile terminals. Many of the proposed solutions rely on consensus-based algorithms, which aim at estimating the configuration of the network via a message passing protocol. In this paper we propose an improved consensus-based distributed camera calibration strategy that exploits a robust initialization, together with a pruning protocol to remove faulty links which could propagate excessively-noisy information through the network reducing the convergence time. The proposed solution seems to improve the state-of-the-art strategies in terms of accuracy, convergence speed, and computational complexity.

Gender-specific medicine is the study of how diseases differ between men and women in terms of prevention, clinical signs, therapeutic approach, prognosis, psychological and social impact. It is a neglected dimension of medicine. In this review we like to point out some major issues in five enormous fields of medicine: cardiovascular diseases (CVDs), pharmacology, oncology, liver diseases and osteoporosis. CVDs have been studied in the last decades mainly in men, but they are the first cause of mortality and disability in women. Risk factors for CVD have different impacts in men and women; clinical manifestations of CVD and the influence of drugs on CVD have lot of gender differences. Sex-related differences in pharmacokinetics and pharmacodynamics are also emerging. These differences have obvious relevance to the efficacy and side effect profiles of various medications in the two sexes. This evidence should be considered for drug development as well as before starting any therapy. Gender disparity in cancer incidence, aggressiveness and prognosis has been observed for a variety of cancers and, even if partially known, is underestimated in clinical practice for the treatment of the major types of cancer. It is necessary to systematize and encode all the known data for each type of tumor on gender differences, to identify where this variable has to be considered for the purposes of the prognosis, the choice of treatment and possible toxicity. Clinical data suggest that men and women exhibit differences regarding the epidemiology and the progression of certain liver diseases, i.e., autoimmune conditions, genetic hemochromatosis, non-alcoholic steatohepatitis and chronic hepatitis C. Numerous hypotheses have been formulated to justify this sex imbalance including sex hormones, reproductive and genetic factors. Nevertheless, none of these hypothesis has thus far gathered enough convincing evidence and in most cases the evidence is conflicting. Osteoporosis is an important public health problem both in women and men. On the whole, far more epidemiologic, diagnostic and therapeutic studies have been carried out in women than in men. In clinical practice, if this disease remains underestimated in women, patients’ and physicians’ awareness is even lower for male osteoporosis, for which diagnostic and therapeutic strategies are at present less defined. In conclusion this review emphasizes the urgency of basic science and clinical research to increase our understanding of the gender differences of diseases.

Background Dialysis and kidney transplantation represent two effective strategies in treating chronic uremia, albeit with different results. Our study compared the psychological aspects of two categories of patients: patients who faced kidney transplantation and have been on dialysis, and noncompliant patients treated with these therapies. Materials and Methods On 170 patients (120 hemodialysis and 50 peritoneal dialysis) we used a personality analysis (MMPI2) and the COPE, which assessed the ability of patients to cope under certain conditions that can be perceived as stressful or, in any case, unusual. The screening succeeded in 11 cases among the first group and 9 in the second. Three of the 20 patients were considered to be partially noncompliant: 1 on peritoneal and the other 2 on hemodialysis. We also tested a control group of 300 people of different ages, sexes, social and cultural status, dates and kinds of transplantation (cadaveric or living donors). Of the 36 feedbacks received, only 30 were considered valuable. Results The results of the research showed that patients with less than 2 years of dialysis treatment and patients with more than 2 years survival after transplantation time were inclined to deny their disease and the possible emotions about their clinical status, drawing an inadequate attention to the difficulties. This behavior was clearer among noncompliant patients. Family problems and couple malaise in everyday life can push more and more of these patients to be noncompliant with therapeutic prescriptions, as they do not feel adequate support. The result is an excessive foreboding, poor disposition, and nervousness. Conclusions Screening of patients’ social and psychological status is useful as is psychological intervention for those who miss emotional support from the family. This psychological support is advisable for uremics who have to enter a waiting list and for those who are subject to postoperative treatment in order to promote compliant behavior.

Gender accounts for important differences in the incidence and prevalence of a variety of age-related diseases. Considering people of far advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In the present investigation, we report data from a nationwide study on Italian centenarians (a total of 1162 subjects), and from two studies on centenarians living in two distinct zones of Italy, i.e., the island of Sardinia (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of 43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of environmental, historical and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. Gender differences in the health status of centenarians are also reported, and an innovative score method to classify long-lived people in different health categories, according to clinical and functional parameters, is proposed. Our data indicate that not only is this selected group of people, as a whole, highly heterogeneous, but also that a marked gender difference exists, since male centenarians are less heterogeneous and more healthy than female centenarians. Immunological factors regarding the age-related increase in pro-inflammatory status, and the frequency of HLA ancestral haplotypes also show gender differences that likely contribute to the different strategies that men and women seem to follow to achieve longevity. Concerning the different impact of genetic factors on the probability of reaching the extreme limits of the human life-span, emerging evidence (regarding mtDNA haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female longevity is less dependent on genetics than male longevity, and that female centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics of the Italian society in the last 100 years.

The aging of the Italian population is an emerging public health priority. In 2025 Italy is expected to have the highest world median age with nearly half of the population over 50 years old. To avoid an unbearable burden of disease and disability on future generations, we must identify areas for intensive disease and disability prevention programs. Preliminary results from the PRO.V.A study show that disability is associated with conditions that are potentially preventable as chronic diseases and falls or are treatable as chronic pains. Moreover, it is of extreme interest to identify and understand biological and environmental secrets of successful aging as the AKEA study tries to do and the ways of overcoming disabilities in the extreme limits of life more and more possible to reach.

Mutations on the apolipoprotein (apo) B gene that interfere with the full-length translation of the apoB molecule are associated with familial hypobetalipoproteinemia (FHBL), a disease characterized by the reduction of plasma apoB and LDL cholesterol. In this report, we describe an FHBL kindred carrying a unique truncated apoB form, apoB-87 Padova . Sequence analysis of amplified genomic DNA identified a single G deletion at nucleotide 12 032, which shifts the translation reading frame and causes a termination at amino acid 3978. Two homozygous subjects and seven heterozygous relatives were studied. Although homozygous individuals had only trace amounts of LDL, they were virtually free from the symptoms typical of homozygous FHBL subjects. We investigated the in vivo turnover of radiolabeled normal apoB-100 LDL and apoB-87 LDL in one homozygous patient and two normal control subjects. ApoB-87 LDL showed a similar metabolism in all three subjects, with a fractional catabolic rate more than double that of normal LDL. The rate of entry of apoB-87 in the LDL compartment was also markedly decreased compared with normal apoB-100. The increased in vivo catabolism of apoB-87 LDL was paralleled in vitro by a 2.5-fold increased ability of these particles to inhibit the uptake and degradation of normal apoB-100 LDL by normal human cultured fibroblasts. These results indicate that apoB-87 LDL has an enhanced ability to interact with the LDL receptor; the increased apoB catabolism contributes to the hypobetalipoproteinemia and may explain the mild expression of the disease in the two homozygous individuals.

The efficacy of the heparin-induced extracorporeal LDL-precipitation (HELP)-apheresis procedure has been studied in an open prospective multicentre trial. After 2 years of regular weekly HELP-treatment the data from 39 of 51 patients could be evaluated according to the study criteria. Twelve of the initially recruited study patients were omitted from the evaluation either because of premature termination of the treatment or because they did not fulfil the exact guidelines of the study protocol. A mean of 2.831 plasma was regularly treated on average every 7.85 days. The mean pre-/post-apheresis LDL-cholesterol levels decreased from 286/121 mg dl-1 at the first HELP treatment to 203/77 mg dl-1 after 1 year and to 205/77 mg dl-1 after 2 years of regular apheresis; the corresponding values for fibrinogen were 314/144, 246/98 and 250/105 mg dl-1, respectively. In contrast, the mean pre-/post-apheresis HDL-cholesterol levels rose from 41/38 through 51/44 mg dl-1 after 1 year to 52/43 mg dl-1 after 2 years of treatment. The overall result was a normalization of the atherogenic index (LDL-/HDL-cholesterol ratio) from 6.9/3.2 to 4.0/1.9. The angiographies from 33 patients obtained before and after 2 years of regular treatment could be evaluated blindly using the cardiovascular angiography analysis system. The mean degree of stenosis of all segments decreased from 32.5% (SD = 16) to 30.6% (SD = 16.8) over the 2 years. A regression > 8% was observed in 50/187 (26.7%) segments, whereas 29/187 (15.5%) segments showed progression. In 108/187 (57.8%) segments the lesions were stable (< 8% deviation) over 2 years. We conclude that regular treatment with HELP-LDL-apheresis is able to stabilize progressive atherosclerotic disease and to induce almost twice as much regression as progression of atherosclerotic lesions.

Legislative decrees 277/91 and 626/94 defined in detail role and duties of the occupational physician. There is no normative regulation about ethical principles for occupational professionals although some international organizations, such as the International Commission on Occupational Health (ICOH), are making proposals in this field. In the last decades, these principles have been assuming an increasing importance because of occupational medicine operators' major responsibility and the need of a multidisciplinary approach in work related risk prevention. The aim of this contribution is to present a case about professional independence and commercial secret that involved an occupational physician (David G. Kern), Brown University (that employees him) Memorial Hospital and a textile firm that consulted dr. Kern to investigate a pulmonary disease that affected some employees. The fact has been described by e-mail of OEM (Occupational Environmental Medicine) list. This event underlines the distance between the professional reality and ethical principles formulated in the ICOH code; these principles must be the base for a correct professional activity aiming only at promoting workers' health.

Gender accounts for important differences in the incidence and prevalence of a variety of age-related diseases. Considering people of far advanced age, demographic data document a clear-cut prevalence of females compared to males, suggesting that sex-specific mortality rates follow different trajectories during aging. In the present investigation, we report data from a nationwide study on Italian centenarians (a total of 1162 subjects), and from two studies on centenarians living in two distinct zones of Italy, i.e., the island of Sardinia (a total of 222 subjects) and the Mantova province (Northern Italy) (a total of 43 subjects). The female/male ratio was about 2:1 in Sardinia, 4:1 in the whole of Italy, and about 7:1 in the Mantova province. Thus, a complex interaction of environmental, historical and genetic factors, differently characterizing the various parts of Italy, likely plays an important role in determining the gender-specific probability of achieving longevity. Gender differences in the health status of centenarians are also reported, and an innovative score method to classify long-lived people in different health categories, according to clinical and functional parameters, is proposed. Our data indicate that not only is this selected group of people, as a whole, highly heterogeneous, but also that a marked gender difference exists, since male centenarians are less heterogeneous and more healthy than female centenarians. Immunological factors regarding the age-related increase in pro-inflammatory status, and the frequency of HLA ancestral haplotypes also show gender differences that likely contribute to the different strategies that men and women seem to follow to achieve longevity. Concerning the different impact of genetic factors on the probability of reaching the extreme limits of the human life-span, emerging evidence (regarding mtDNA haplogroups, Thyrosine Hydroxilase, and IL-6 genes) suggests that female longevity is less dependent on genetics than male longevity, and that female centenarians likely exploited a healthier life-style and more favorable environmental conditions, owing to gender-specific cultural and anthropological characteristics of the Italian society in the last 100 years.

Some N-sulphonated-2-substituted benzimidazoles and imidazo[4,5-b]-pyridines were synthesized and tested in vitro for antiviral and antiproliferative activity. None of the compounds had antiviral properties. However, three of them inhibited the proliferation of leukaemia and lymphoma cell lines at micromolar concentrations. The maximum potency of antiproliferative activity is correlated with the presence of an ethylenic spacer between the two heterocycles.

The possibility that four loci (REN, THO, PARP, SOD2) are associated with longevity was explored by comparing the genotypic pools of subjects older than 100 years with those of younger subjects matched for sex and geographic area (northern and southern Italy). The markers (all located within the respective gene) were HUMREN4; HUMTHO1; HUMPARP (gt)845nt; SOD2(C/T)401nt. In order to reduce the number of genotypes, multiallelic polymorphisms were recoded as diallelic according to allele size and frequency patterns (small: S, and large: L, alleles). A significant loss of LL homozygous genotypes was found at the THO locus in male but not in female centenarians with respect to matched controls. On the other hand no significant difference was found between case/control genotypic frequencies at REN, PARP, SOD2 loci. The latter loci therefore do not affect inter-individual variability in life expectancy (at least in terms of qualitative variants associated with the tested markers). However, the data is consistent with an association between the THO locus and longevity.

Mitochondrial DNA (mtDNA) is characterized by high variability, maternal inheritance, and absence of recombination. Studies of human populations have revealed ancestral associated polymorphisms whose combination defines groups of mtDNA types (haplogroups) that are currently used to reconstruct human evolution lineages. We used such inherited mtDNA markers to compare mtDNA population pools between a sample of individuals selected for successful aging and longevity (212 subjects older than 100 years and in good clinical condition) and a sample of 275 younger individuals (median age 38 years) carefully matched as to sex and geographic origin (northern and southern Italy). All nine haplogroups that are typical of Europeans were found in both samples, but male centenarians emerged in northern Italy as a particular sample: 1) mtDNA haplogroup frequency distribution was different between centenarians and younger individuals (P=0.017 by permutation tests); and 2) the frequency of the J haplogroup was notably higher in centenarians than in younger individuals (P=0.0052 by Fisher exact test). Since haplogroups are defined on the basis of inherited variants, these data show that mtDNA inherited variability could play a role in successful aging and longevity.

Human longevity is a multifactorial trait, which includes a network of genes combined with strong environmental factors. Biological and clinical characteristics of human beings are the result of the interaction between genes and the environment. Until about 1950 centenarians were quite rare in low-mortality countries. Since then the number has more than doubled every 10 years and even the number of 105+ year old people is now increasing. This proliferation of centenarians is mainly a result of the decrease in oldest-old mortality and probably due to changes of lifestyle and health care. Although studies of Danish twin pairs seem to indicate that genetic influence on human lifespan is only moderate, several gene loci contribute to longevity. Data are evident from the Italian Centenarian Study for apoproteinB, tyrosine hydroxylase and mitochondrial DNA loci among others studied (superoxide dismutases, ie. SOD1 and SOD2, poly(ADP-ribose)polymerase and thyroid peroxidase). The data from the Danish Centenarian Study confirm the findings from the studies of French and Finnish centenarians on apolipoprotein E genotype with a higher frequency of epsilon-2 and lower frequency of epsilon-4. However, the apoE genotype seems not to be a key determinant of exceptional longevity: in 105+ year olds the epsilon-4 allele was found in 4 out of 19 persons. Italian centanarians have a paradoxically marked hypercoagulability as demonstrated also by genetic markers. Also the von Willebrand factor was increased independently of the blood group. Studies on such atherosclerosis risk factors as lipoprotein(a) and homocysteine revealed that these two parameters may be high in Italian centenarians, but their genetic control possibly attenuates with age, and environmental factors may play a major role in the oldest-old persons. Also interaction among genes is possible. All these studies suggest that longevity is a phoenomenon depending on multiple genetic and environmental factors. Further studies are needed for a better understanding of the complex interactions which allow people to reach a very old age.

In this study, the apolipoprotein E (apoE) genotypes as well as plasma lipid and lipoprotein levels have been determined for the first time in 633 healthy and unrelated inhabitants on the island of Sardinia (291 men and 342 women, age range 6-89 years), randomly selected in the four districts of Sardinia among healthy people having parents and grandparents born in the same geographic area. This island lies in the centre of the western Mediterranean sea with a well-recognized peculiar and preserved genetic background. The epsilon 3 allele frequency (0.897) is higher than that previously reported in southern and mainland Italy and is one of the highest in Europe and among Caucasians; epsilon 2 allele frequency (0.040) is the lowest in Europe; epsilon 4 (0.063) is unusually low and, most interestingly, does not change in the different age groups, i.e. does not decrease in old subjects.Lipid and lipoprotein analysis confirm that total cholesterol and low-density lipoprotein (LDL)-cholesterol levels are lower than those described in mainland Italy; moreover, in this large Sardinian series, accurately selected, epsilon 4 allele did not influence total cholesterol (P = 0.270), LDL-cholesterol (P = 0.667) and high-density lipoprotein (HDL)-cholesterol (P = 0.549) as in other populations. In contrast, subjects carrying the epsilon 2 allele were found to have significantly lower total cholesterol (P = 0.001) and LDL-cholesterol (P = 0.001) levels than epsilon 3 carriers.The low epsilon 4 frequency and the lack of influence of this allele on lipid metabolism is a unique characteristic and, to date, has been described only in Sardinia among Caucasians; it might contribute to the low prevalence of coronary artery disease in this island.

The most widely-known anti-tumor drugs often induce marked immunosuppression which can give rise to one or more sepses. Anti-infection measures immediately applied can sometimes prove largely ineffective or even useless, the patient dying not as a result of the spread of the tumour but as a direct consequence of opportunistic infection. We postulate that antagonism between anti-tumour and antimicrobial drugs may also play an important part in this. By way of illustration of this hypothesis, we have studied the action of a number of known inhibitors of peptidoglycan synthesis and of DNA-gyrases on certain strains of Gram-positive and Gram-negative microorganisms cultured in medium containing various concentrations of some of the best-known anti-tumour antimetabolites. The experimental data show that antimicrobial and anti-tumour drugs can sometimes induce synergic or indifferent chemotherapeutic interactions with many bacteria, while in others the effect is antagonistic. In practice, the action of the drugs could lead to bacterial selectivity, which, in conjunction with immunosuppression and the presence of resistant strains, could favour the evolution of opportunistic infection.

Substances like imidazoles, benzimidazoles and also quinolines, whose chemical structure includes a heterocyclic nitrogen, are known to interfere with the microsomal oxidation and, in some cases, with the metabolism of drugs. Since chloroquine and primaquine exert this effect in vivo and in vitro, we studied the influence of other antimalarials (quinine and mepacrine) in mice with induced Ehrlich ascites tumour (EAT) to find out whether variations in oxygen consumption affected the course of the disease. In vitro data, obtained by a polarographic technique, indicate that primaquine and, in particular, mepacrine increase EAT-cell oxygen consumption, while in vivo data, obtained in mice injected with an inoculum of about 1 x 10(6) tumour cells per mouse, show that both drugs, but notably mepacrine, accelerate tumour growth, as monitored by Cox's statistical method for body weight, and lead to earlier death. In cases of existing neoplasia, therefore, the potentially toxic effects of certain antimalarials must be borne in mind.

It has been demonstrated that 18 alpha-glycyrrhetinic acid, 18 beta-glycyrrhetinic acid and glycyrrhizin effectively inhibit the inception and growth of skin tumours. Moreover, glycyrrhizin and its aglycone act on the growth and differentiation of mouse melanoma cells in culture. In this study we investigated the effect of glycyrrhizin, 18 alpha- and 18 beta-glycyrrhetinic acids on the evolution of Ehrlich ascites tumour in mice. A prolonged glycyrrhizin treatment proved to be effective in modifying the animals' survival pattern.

We have investigated the effects of the H2 receptor antagonist roxatidine on the neuromuscular transmission by using the sciatic nerve-gastrocnemius muscle preparation of the rat in vivo. Roxatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on the preparation stimulated at high frequency. The neuromuscular blockade induced by roxatidine is partially reversed by 4-aminopyridine but not by dimaprit.

Recent clinical and toxicological studies have investigated the mineralcorticoid-like and hypertensive effects of liquorice, and we therefore set out to identify the active component responsible for these effects. We conducted a 30-day comparative analysis of glycyrrhizin and 18 beta-glycyrrhetinic acid and found that the latter causes significant variations both in systolic blood pressure and in the excretion in the urine of Ca++. The effects were fully reversible on suspension of treatment.

The effect of the H2-receptor antagonist, nizatidine, on neuromuscular transmission was investigated using sciatic nerve-gastrocnemius muscle preparations of rat in vivo. Nizatidine, administered by i.v. injection, potentiates the neuromuscular blockade induced by d-tubocurarine, pancuronium and the aminoglycoside antibiotic, kanamycin. Moreover, the drug alone is capable of producing a blockade on preparations stimulated at high frequency. The neuromuscular blockade induced by nizatidine is reversed by 4-aminopyridine but not by dimaprit.

The major cause of death in older individuals is cardiovascular disease (CVD), responsible for about 50% of the total mortality in most western countries [42]. CVD also accounts for significant health costs and is a major cause of disability in older people; its incidence and prevalence rise progressively with age in both sexes, particularly in older women. Therefore, the substantial advantage experienced by younger women compared to men disappears at advanced ages. The male to female ratio for CVD mortality declines from 2.6 in the age group 55–64 years to 1.1 in the individuals 75 years and older [42].

From September 1975 to December 1986, 115 consecutive previously untreated patients with multiple myeloma (MM) were treated with combination chemotherapy consisting of BCNU, cyclophosphamide, melphalan, vincristine, and prednisone (M-2). No patients were excluded or lost during follow-up. Forty-three percent of the patients were Stage I plus II, and 57% were Stage III. Thirty-eight patients (33%) had blood urea nitrogen greater than or equal to 40 mg/dl (substage B). Reaching an objective response treatment was stopped, generally after 1 year, and restarted at relapse. After induction therapy, 94 patients (82%) responded and had a median duration of response (MDR) of 22 months. After first relapse, 26 of 38 patients (69%) responded again to the same regimen and had an MDR of 11 months. This response rate and MDR are significantly lower than the ones achieved in induction chemotherapy. After second relapse, 7 of 16 patients (44%) again responded with an MDR of 3.5 months. The median survival time (MST) was 50.5 months for all patients. The most relevant side effect was leukopenia. No case of secondary leukemia was noticed. The authors conclude that patients with MM can be treated safely without maintenance therapy after reaching remission because a high response rate can be obtained in first and even second relapse. The planned treatment pause at remission does not adversely affect the survival time. Secondary leukemia is infrequent after this policy. Quality of life improves during the treatment pause.

This study compared the efficacy and safety of pravastatin and gemfibrozil in the treatment of primary hypercholesterolemia. Three hundred eighty-five outpatients from 13 lipid clinics in Italy participated in this randomized double-blind study. Patients were assigned to receive either 40 mg once daily of pravastatin or 600 mg of gemfibrozil twice daily after an initial diet lead-in period. After 24 weeks, mean reductions from baseline values of plasma total and low-density lipoprotein cholesterol were, respectively, 23% and 30% with pravastatin and 14% and 17% with gemfibrozil. Significant lipid-lowering effects were noted within 4 weeks. Apolipoprotein B decrease was 21% with pravastatin and 13% with gemfibrozil. A statistically significant increase of high-density lipoprotein cholesterol of 5% was achieved with pravastatin compared with a 13% increase for gemfibrozil. Serum triglyceride values decreased 5% with pravastatin and 37% with gemfibrozil. Familial and polygenic hypercholesterolemic patients were also examined separately. Pravastatin effectiveness in reducing low-density lipoprotein cholesterol was greater by 6% in polygenic than in familial hypercholesterolemic patients. Treatment for 25 patients (eight treated with pravastatin and 17 treated with gemfibrozil) was discontinued during the study. The incidence of clinical symptoms and laboratory alterations was low for both treatment groups. Pravastatin and gemfibrozil were well tolerated, but pravastatin was significantly more effective in reducing total and low-density lipoprotein cholesterol levels in primary (either familial or polygenic) hypercholesterolemias than gemfibrozil.

Apolipoprotein (apo) C-II plays a central role in normal triglyceride metabolism as cofactor for the enzyme lipoprotein lipase (LPL). Patients with a deficiency of either apoC-II or LPL have marked derangements in triglyceride metabolism which include an elevation of plasma triglycerides, fasting chylomicrons and VLDL (1). Clinical features of this syndrome, which is inherited as an autosomal recessive trait, include hepatosplenomegaly, eruptive xanthomas and an increased risk of pancreatitis. The diagnosis of apoC-II or LPL deficiency is established by finding a reduced post-heparin lipoprotein lipase activity which in apoC-II deficiency is corrected by the addition of normal apoC-II containing plasma.

The mechanism of the contractile effect of dopamine (DA) on the rat isolated seminal vesicle was studied. Cocaine (10 microM/1 in the organ bath, 30 min before DA) and 6-OHDA (50 mg/kg i.v. 24 hr before removal of the seminal vesicle) almost completely prevented the contractile effect of DA. Drugs known to have an affinity for DA receptors or for alpha-adrenoceptors antagonized the contractile effect of DA, the rank order of potency being: prazosin greater than phentolamine greater than yohimbine greater than clonidine greater than sulpiride greater than apomorphine greater than haloperidol. The antagonism was in each case greater against DA than against noradrenaline (NA), used for comparison; selectivity for DA being highest in the case of prazosin and sulpiride. Taken together, these findings indicate that DA makes the rat seminal vesicle contract mostly by means of an indirect mechanism, binding presynaptic DA-receptors and, in part, presynaptic alpha-adrenoceptors as well; or, alternatively, binding presynaptic DA-receptors which have some links with alpha 2-adrenoceptors; the consequence being in either case the release of NA from sympathetic nerve endings.

The influence of the free radical scavenger 2,4-tetra-O-methyl-furfurylidene-sorbitol (MSF) on the carrageenan-induced hind-paw inflammation in rats as well as its influence on the anti-inflammatory and toxic activities of indomethacin is evaluated in comparison with thiola, thioctic acid, silymarin, reduced glutathione and propylgallate. MSF has been previously shown to prevent, in rats, the liver damaging effects of CCl4, ethionine, allylic alcohol and amanita phalloides row extracts. MSF, but not the other scavengers, exhibits moderate anti-inflammatory properties and markedly potentiates the anti-inflammatory activity of indomethacin. Further MSF, but not the other scavengers, reduces some expressions of indomethacin toxicity such as gastric mucosal damage, intestinal hemorrhage and peritoneal fluid accumulation and ensuing death. Since MSF shares a number of pharmacological properties with vitamin E, which also increases indomethacin anti-inflammatory activity while reducing indomethacin toxicity, it is suggested that MSF has this for its vitamin E-like activity perhaps as a result of altering the arachidonic acid cascade.

In this study it is demonstrated, that incubation of both, bile acids and free fatty acids with LP-X, the abnormal plasmalipoprotein found in patients suffering from cholestasis or LCAT-deficiency, results in striking alterations of the physico-chemical and immunological properties of LP-X: 1. The cathodic mobility in agar is changed into an anodic mairation of the material. 2. The unique appearance of LP-X on electronmicrographs is altered by the incubation revealing fingerprint like structures. 3. The albumin portion of LP-X becomes immunologically detectable. 4. Bile salts cause marked changes in the hydrated density of the material as determined by zonal ultracentrifugation. 5. In vitro incubation of LP-X with postheparin plasma causes a complete disappearance of LP-X as judged by its typical migration on agar electrophoresis. All these alterations can be prevented or reversed by the addition of albumin in appropriate concentrations. These findinga are important in the light of studies designed to investigate the catabolic action of plasma lipolytic enzymes on LP-X, as well as for follow up studies of LP-X concentrations during the course of disease.

The use of calcium antagonists such as nifedipine for myocardial protection during cardiac surgery has been advocated by several authors. During extracorporeal circulation many factors, such as light, interaction with circuit materials and haematocrit, may contribute to decrease plasma clearance of calcium antagonists In an in vitro model of a heart-lung machine, plasma nifedipine and prime concentrations were detected with a series of samples at different temperatures (25 °C and 37 °C), haematocrits (0%, 20%, 30% and 40%) and light conditions (light and dark). The results show a rapid drop of nifedipine concentration with a halflife of about 3-9 minutes and this situation is influenced with statistical significance by the presence of light and increased haematocrit. The knowledge of this condition is useful when nifedipine is used before/ during cardiopulmonary bypass and during cardioplegia and reperfusion infusion with the use of extracorporeal devices.

The apo C-II gene from a patient with apo C-II deficiency has been sequenced after amplification by the polymerase chain reaction. A substitution of an adenosine for a guanosine at position 3002 in exon 3 of the patient's gene was identified by sequence analysis. This mutation leads to the introduction of a premature termination codon (TAA) at a position corresponding to amino acid 37 of mature apo C-II and to the formation of a new Rsa I restriction enzyme site not present in the normal apo C-II gene. Amplification of DNA from family members by the polymerase chain reaction and digestion with Rsa I established that the patient is a true homozygote for the mutation. Analysis of the patient's plasma by two-dimensional gel electrophoresis and immunoblotting detected an apo C-II that exhibited abnormal electrophoretic mobility. We propose that the C to A substitution in the apo C-IIPadova gene is the primary genetic defect that leads to premature termination and the synthesis of a truncated 36 amino acid apo C-II that is unable to activate lipoprotein lipase.

In vitro incubation of pig bile with pig whole serum resulted in the formation of “LP-X like” material migrating towards the cathode on agar-gel electrophoresis. As in all other species studied so far, LP-X occurred also in the serum of bile duct ligated pigs, however, relatively late (48–72 h) after the operation. In parallel, alterations of some serum parameters and of the protein-lipid composition of the different lipoprotein fractions were observed. While the electrophoretic behaviour, the protein-lipid and apoprotein composition of pig LP-X were comparable to those found in man, dog and rat, it sedimented in most instances at the density 1.063 g/ml.

Adult male rats were treated intraperitoneally (IP) with imidazole (IMID), distilled water or saline prior to administration of lisuride either IP or intracerebroventricularly (ICV) at doses too low by themselves to elicit the behavioural signs of mounting and aggressiveness, typically induced by higher doses of this drug. Pretreatment with distilled water or saline, or the procedure of injection alone, stimulated mounting in some of the animals. At a certain range of doses IMID induced a marked increase in both mounting and aggressive posturing in the same animals, while at higher doses mounting ceased, violent aggressive behaviour appeared and some of the rats died. Seven IMID derivatives were used on the lisuride-test: N-methylimidazole, 2-methylimidazole, 4-methylimidazole, N-acetylimidazole, 4-imidaaoleacetic acid, clonidine and cimetidine. Only 4-imidazoleacetic acid was completely ineffective with respect to controls. All the other drugs enhanced aggressive behaviour to varying degrees but proved to be less potent than IMID in inducing mounting, and clonidine reduced mounting at all the doses tested.

B-HT 920, a selective agonist at dopamine (DA) autoreceptors, strongly increased the incidence of penile erections (PE) in male rats, an effect which was dose-related and antagonized by haloperidol. B-HT 920 at 100 and 200 micrograms/kg i.p. significantly altered the copulatory pattern of sexually active male rats, reducing the number of mounts and intromissions as well as the latency to the first ejaculation, a stimulant effect which was confirmed in sluggish males at a dose of 100 micrograms/kg.