Entourage effect for phenolic compounds on production and metabolism of mammary epithelial cells.

Primary culture of mammary epithelial cells (MEC) was exposed to ethyl-acetate, chloroform and hexane extracts of Pistacia lentiscus (lentisk). The hexane extract contained mainly ethyl gallate whereas the chloroform extract contained mainly ethyl-gallate with smaller amount of gallic acid, and the ethyl-acetate extract contained mainly rutin, gallic acid and myricetin. Ethyl acetate extract increased secretion of protein and fat and improved mitochondrial activity. The enhancing effect on protein production was attributed to myricetin, one of the polyphenols in the ethyl-acetate extract whereas gallic acid did not affect protein production or secretion. Interestingly, exposure to the isolated polyphenols did not improve mitochondrial productivity and activity as effectively as exposure to the complete plant extract. The results indicated that polyphenols improve production of milk constituents by MEC, through different modes of action for different polyphenols suggesting an additive or even synergistic effect on production traits of mammary cells.

Pistacia lentiscus extract enhances mammary epithelial cells' productivity by modulating their oxidative status.

We assessed the potential of phenolic compounds from Pistacia lentiscus (lentisk) to enhance production of milk constituents in bovine mammary epithelial cells (MEC). MEC were exposed to 0 (control), 1 or 10 ppm of polyphenols from lentisk ethanolic extract (PLEE) for 24 h. PLEE were absorbed by the MEC plasma membrane, but also penetrated the cell to accumulate in and around the nucleus. PLEE increased triglyceride content in the cell and its secretion to the medium, and significantly increased intracellular lipid droplet diameter. Compared to control, PLEE increased dose-dependently the lactose synthesis, secretion of whey proteins, and contents of casein. To evaluate mitochondrial activity under pro-oxidant load, MEC were preincubated with PLEE and exposed for 2 h to H2O2. Exposure to H2O2 increased the proportion of cells with impaired mitochondrial membrane potential twofold in controls, but not in PLEE-pre-treated cells. Accordingly, proton leakage was markedly decreased by PLEE, and coupling efficiency between the respiratory chain and ATP production was significantly enhanced. Thus, lentisk polyphenols divert energy to production of milk fat, protein and lactose, with less energy directed to cellular damage control; alternatively, PLEE enables MEC to maintain energy and oxidative status under extreme metabolic rate required for milk production and secretion, and reduces the limitation on energy required to support production.

Dual effect of spermine on acrosomal exocytosis in capacitated bovine spermatozoa.

The influence on spermine on the acrosomal exocytosis of capacitated bovine spermatozoa was studied. Dual effect of spermine was observed, depending on its concentration. It was shown that 10 microM spermine stimulated acrosomal exocytosis and prostaglandin F2 alpha production, whereas higher concentrations of spermine inhibited these processes. Acrosomal exocytosis induced by spermine was inhibited by staurosporine, a specific protein kinase C (PKC) inhibitor, indicating that PKC may be involved in this stimulation. Also, acrosomal exocytosis induced by the PKC activator phorbol 12-myristate-13-acetate was inhibited by 10 mM spermine. Therefore, these data indicate that spermine is involved in signal transduction events leading to exocytosis. We suggest that the concentration-dependent reversal of the stimulatory action of spermine could be explained by the existence of two binding sites for spermine: high affinity sites involved in inducing acrosomal exocytosis by low spermine concentration and low affinity sites mediating inhibition of acrosomal exocytosis by high concentration of spermine.

Echocardiographic demonstration of decreased left ventricular dimensions and vigorous myocardial contraction during syncope induced by head-up tilt.

Two-dimensional echocardiography was performed during a head-up tilt test in 11 control subjects (group I) and 18 patients with recurrent unexplained syncope. In four patients (group II), the head-up tilt test was negative at baseline and after isoproterenol infusion. Syncope was induced during baseline head-up tilt in nine patients (group III) and after isoproterenol challenge in five (group IV). The echocardiographic variables assessed were left ventricular end-systolic and end-diastolic areas and percent fractional shortening. At the end of head-up tilt, end-systolic area decreased by 4.5 +/- 1.3 and 3.0 +/- 1.2 cm2 in groups III and IV, respectively, compared with 0.5 +/- 0.7 and 0.2 +/- 0.1 cm2 in groups I and II, respectively (p less than 0.04). Similarly, end-diastolic area decreased by 5.5 +/- 2.6 cm2 in group III compared with 2.7 +/- 1.9 and 1.75 +/- 0.4 cm2 in group I and II, respectively (p less than 0.04). Additionally, at the end of the baseline study, fractional shortening was significantly greater in group III and group IV (43 +/- 5%) than in groups I and II (p less than 0.01). In conclusion, syncope induced by head-up tilt is associated with vigorous myocardial contraction and a significant decrease in left ventricular end-systolic dimensions. This left ventricular hypercontractility may play an important role in the pathogenesis of syncope induced by head-up tilt.

Does the electrocardiographic pattern of "anteroseptal" myocardial infarction correlate with the anatomic location of myocardial injury?

The current electrocardiographic (ECG) definition of anteroseptal acute myocardial infarction (AMI) is a Q wave or QS wave > 0.03 second in leads V1 to V3, with or without involvement of lead V4. To verify whether there is a correlation between the ECG pattern of anteroseptal AMI and the location of an AMI, we compared ECG, echocardiographic, and cardiac catheterization findings of 80 patients who fit the traditional definition of anteroseptal AMI. We found that 48 of 52 patients (92%) who presented with ST elevation in leads V1 to V3 had an anteroapical infarct and a normal septum. The culprit narrowing was more frequently found (in 85% of patients) in the mid to distal left anterior descending artery. We conclude that there is no correlation and that the ECG pattern traditionally termed anteroseptal AMI should be called an anteroapical AMI; the term anteroseptal AMI should be defined as extensive anterior wall AMI associated with diffuse ST changes involving the anterior, lateral, and occasionally, inferior leads.

HLA-Dw"SHY": a new lymphocyte defined specificity associated with HLA-DRw10.

HLA-DRw10 is a relatively new class II serologically-defined alloantigen first described in the 8th International Histocompatibility Workshop. To date the HLA-Dw related to the DRw10 specificity has not been detected. We have studied a Jewish family ("SHY") of Yemenite origin, in which the parents are first cousins who share one HLA haplotype: A29,Cw2,B7,BfF,DRw10,GL02. Two of the offspring in this family are homozygous for this haplotype. MLC family study confirmed that each of the two individuals was homozygous for HLA-Dw. No currently defined HLA-Dw specificity could be assigned to "SHY" using a selected panel of Caucasoid and local HTcs. HLA-Dw"SHY" was shown to segregate with DRw10 positive/Dw blank haplotypes in two families and in 64% (7/11) of DRw10 positive unrelated positive/Dw blank haplotypes in two families and in 64% (7/11) of DRw10 positive unrelated individuals. HTC"SHY" thus expresses the first HLA-Dw specificity associated with DRw10.

A new approach for the treatment of interstitial pregnancy.

The surgical treatment of interstitial pregnancy consists of either cornual resection or hysterectomy, which may seriously impair future fertility. We report a new approach that avoids surgical intervention. This presents a major breakthrough in the management of interstitial pregnancy.

Progressive cutaneous herpes simplex infection in acute myeloblastic leukemia. Successful treatment with interferon and cytarabine.

A patient had acute myeloblastic leukemia and extensive progressive cutaneous herpes simplex virus infection. Complete and rapid healing of skin lesions with remission of the leukemia occurred during 15 days of therapy with human leukocyte interferon and minimal doses of cytarabine hydrochloride. Pharmacokinetic studies showed that the patient had a defective antiviral interferon response, which was effectively corrected by treatment with interferon alpha. This may help to explain the dramatic response of both conditions to therapy.

Mitral regurgitation: parameters that affect the correlation between Doppler echocardiography and contrast ventriculography.

The correlation between Doppler and contrast angiographic estimation of severity of mitral regurgitation was assessed retrospectively in 60 patients with native mitral valve disease. Results showed r = 0.82. Among 15 parameters (demographic, clinical, echocardiographic and hemodynamic) 3 were found to be associated with overestimation of the severity by Doppler: low left ventricular ejection fraction, low cardiac output, and high mean pulmonary artery capillary wedge pressure. On the other hand, a large left atrium was associated with underestimation of mitral regurgitation by Doppler. Based on that data, Doppler results were adjusted in a prospective group of 30 patients with native mitral valve disease. The correlation between contrast ventriculography and uncorrected Doppler results showed r = 0.83, while the corrected Doppler results showed r = 0.91. The study implies that although a good correlation is found between the two modalities for estimation of mitral regurgitation, a better correlation can be achieved by adjusting the Doppler results according to the above-mentioned parameters.

Complete atrioventricular block in Shone's syndrome.

A rare case of an adult patient with Shone's syndrome is presented in whom Lev's disease seems to be the major pathology underlying the development of complete A-V block.

Long-term prognostic value of a normal dipyridamole thallium-201 perfusion scan.

In a 4-year period, 84 patients who were referred for a dipyridamole thallium-201 stress test to rule out significant coronary artery disease had normal scans. A dipyridamole study was recommended instead of exercise because of arthritis, severe obesity, peripheral vascular disease, pulmonary disease, other chronic illnesses, or combinations of these problems. All patients had three-view (i.e., anterior, shallow left anterior oblique, and steep left anterior oblique) planar thallium-201 imaging 10 minutes and 3.5 hours after administration of 0.6 mg/kg of intravenous dipyridamole. The patients were followed for 42 +/- 13 (range 1-58) months to document the cardiac event rate. Of the 84 patients with normal results, 14 died during the follow-up period from noncardiac causes. Three other patients died 29-51 months after the test due to an acute myocardial infarction, a probable acute myocardial infarction, and sudden cardiac death, respectively. Of the survivors, 5 suffered an acute myocardial infarction 28-50 months after the dipyridamole thallium scan and 1 had coronary artery bypass grafting due to increasing angina pectoris 58 months after the scan (overall cardiac event rate of 0.4% per year). Of the remaining 61 patients, 39 (64%) were asymptomatic, 20 (33%) had the same symptoms they had at the time of testing without significant deterioration, while 2 patients (3%) had deterioration of their chest pains but no cardiac complication. Thus, in this group of patients, a normal dipyridamole thallium-201 perfusion scan predicted a good cardiovascular outcome for at least 24 months following the test.

Successful delivery following myocardial ischemia during the second trimester of pregnancy.

Acute myocardial infarction during pregnancy is considered to be associated with approximately 50% mortality of both mother and fetus. However, there are not enough data regarding the role of acute myocardial ischemia. We present a 36-year-old, pregnant, white female who was admitted twice at 18 and 20 weeks of gestation with acute myocardial ischemia. Cardiac catheterization revealed 70-80% stenosis of the mid left anterior descending artery (LAD) with normal antegrade flow and very good retrograde filling of the LAD from distal collaterals of the right coronary artery. Therefore, due to angiographic suggestion of protected LAD territory, we recommended medical therapy and scheduled a vaginal delivery that was successfully completed without cardiovascular complications. A stress thallium test performed 6 months later was normal, supporting our clinical judgment. In conclusion, every case of a pregnant woman with coronary insufficiency should be treated according to individual coronary anatomy and blood supply to the territory of the diseased artery, and should not be based on the old data in the literature. The decision for revascularization prior to delivery versus medical therapy, or Caesarean section versus natural delivery, should be made by a team of a cardiologist and an obstetrician.

Pre-operative ultrasonographic evaluation of nongravid, enlarged uteri--correlation with bimanual examination.

OBJECTIVE: To correlate the size of the nongravid uterus measured by ultrasound and bimanual examination before hysterectomy, with the actual size of the specimens. PATIENTS AND METHODS: Uterine size of 49 consecutive patients, who underwent elective hysterectomy, was assessed by bimanual pelvic examination, preoperative ultrasonographic evaluation and actual postoperative size. RESULTS: All preoperative ultrasonographic uterine dimensions significantly correlated with the corresponding actual dimensions of the uterine specimens. Furthermore, ultrasonographic uterine length had the best correlation with uterine size estimation by bimanual examination. A formula was established in an attempt to calculate clinical uterine size by gestational week, using preoperative ultrasonographic dimensions. CONCLUSIONS: By using the aforementioned formula, ultrasonographic uterine dimensions can be extrapolated to uterine size in terms of gestational week, and therefore, be applicable to traditional clinical practice.

Pregnancy outcome in women with primary renal disease.

BACKGROUND: The preconception and intraconception parameters that are relevant to outcome in women with underlying renal disease remain controversial. OBJECTIVES: To analyze the types and frequencies of short- and long-term (2 years after delivery) maternal and neonatal complications in 38 patients with primary renal disease (46 pregnancies), most of them with mild renal insufficiency. METHODS: Logistic regression models were formulated to predict successful outcome. RESULTS: Successful pregnancy outcome (live, healthy infant without severe handicap 2 years after delivery) was observed in 98% of the patients with primary renal disease. Factors found to be significantly predictive of successful outcome were absence of pre-existing hypertension, in addition to low preconception serum uric acid level. CONCLUSIONS: Most women with primary renal disease who receive proper prenatal care have a successful pregnancy outcome. Worse pregnancy outcome was observed in women with moderate or severe renal failure. Fitted logistic models may provide useful guidelines for counseling women with preexisting renal disease about their prospects for a successful pregnancy in terms of immediate and long-term maternal and neonatal outcome.

Vaccination against influenza in rheumatoid arthritis: the effect of disease modifying drugs, including TNF alpha blockers.

OBJECTIVE: To assess the efficacy and safety of vaccination against influenza virus in patients with rheumatoid arthritis, with special emphasis on the effect of disease modifying antirheumatic drugs (DMARDs), including tumour necrosis factor alpha (TNFalpha) blockers. METHODS: 82 rheumatoid patients and 30 healthy controls were vaccinated with a split-virion inactivated vaccine containing 15 mug haemagglutinin (HA) per dose of each of B/Hong Kong/330/2001 (HK), A/Panama/2007/99 (PAN), and A/New Caledonian/20/99 (NC). Disease activity was assessed by tender and swollen joint count, morning stiffness, evaluation of pain, Health Assessment Questionnaire, ESR, and C reactive protein on the day of vaccination and six weeks later. Haemagglutination inhibiting (HI) antibodies were tested by a standard WHO procedure. Response was defined as a fourfold or more rise in HI antibodies six weeks after vaccination, or seroconversion in patients with a non-protective baseline level of antibodies (<1/40). Geometric mean titres (GMT) were calculated to assess the immunity of the whole group. RESULTS: Six weeks after vaccination, a significant increase in GMT for each antigen was observed in both groups, this being higher in the healthy group for HK (p=0.004). The percentage of responders was lower in rheumatoid patients than healthy controls (significant for HK). The percentage of responders was not affected by prednisone or any DMARD, including methotrexate, infliximab, and etanercept. Indices of disease activity remained unchanged. CONCLUSIONS: Influenza virus vaccine generated a good humoral response in rheumatoid patients, although lower than in healthy controls. The response was not affected by the use of prednisone or DMARDs.

Modulation of prostaglandin synthesis in mammalian sperm acrosome reaction.

Exogenous arachidonic acid induces the acrosome reaction and the production of the prostaglandins PGE2 and PGF2 alpha in bovine spermatozoa. Exogenous PGE2 also induces the acrosome reaction and PGF2 alpha synthesis. To understand better the role of PGE2 in the induction of PGF2 alpha synthesis through modulation of phospholipase A2, inhibitors of this enzyme were used. The effects of PGE2 were blocked by phospholipase A2 inhibitors and this inhibition was reversed by addition of arachidonic acid. These data indicate that PGE2 activates phospholipase A2 to produce arachidonic acid. To determine whether protein kinase C modulates phospholipase A2 activity in this process, staurosporin, an inhibitor of protein kinase C, was used. The effect of PGE2 on PGF2 alpha production is inhibited by staurosporin and this inhibition was reversed by addition of arachidonic acid indicating that protein kinase C is involved in phospholipase A2 activation. The effect of exogenous arachidonic acid or PGE2 on the acrosome reaction is blocked by lipoxygenase inhibitors but not by inhibitors of cyclo-oxygenase, indicating that lipoxygenase products are involved in the mechanism of the acrosome reaction. The presented data shed light on the cross-talk between cyclo-oxygenase and lipoxygenase and their involvement in the sperm acrosome reaction. It is suggested that cyclo-oxygenase products modulate the activity of lipoxygenase which is a key enzyme in the mechanism leading to the acrosome reaction. Stimulation of cyclo-oxygenase to synthesize PGE2 activates phospholipase A2 to release arachidonic acid which is the substrate for lipoxygenase activity.(ABSTRACT TRUNCATED AT 250 WORDS)