Glutamate optimizes enzymatic activity under high hydrostatic pressure in Desulfovibrio species: effects on the ubiquitous thioredoxin system.

In piezophilic microorganisms, enzymes are optimized to perform under high hydrostatic pressure. The two major reported mechanisms responsible for such adaptation in bacterial species are changes in amino acids in the protein structure, favoring their activity and stability under high-pressure conditions, and the possible accumulation of micromolecular co-solutes in the cytoplasm. Recently, the accumulation of glutamate in the cytoplasm of piezophilic Desulfovibrio species has been reported under high-pressure growth conditions. In this study, analysis of the effect of glutamate on the enzymatic activity of the thioredoxin reductase/thioredoxin enzymatic complex of either a piezosensitive or a piezophilic microorganism confirms its role as a protective co-solute. Analysis of the thioredoxin structures suggests an adaptation both to the presence of glutamate and to high hydrostatic pressure in the enzyme from the piezophilic strain. Indeed, the presence of large surface pockets could counterbalance the overall compression that occurs at high hydrostatic pressure to maintain enzymatic activity. A lower isoelectric point and a greater dipolar moment than that of thioredoxin from the piezosensitive strain would allow the protein from the piezophilic strain to compensate for the presence of the charged amino acid glutamate to interact with its partner.

Polarization of PPD-specific T-cell response of patients with tuberculosis from Th0 to Th1 profile after successful antimycobacterial therapy or in vitro conditioning with interferon-alpha or interleukin-12.

The T helper (Th) 1/Th2 balance in the T-lymphocyte response to purified protein derivative (PPD) was evaluated at the clonal level in six Italian and five Gambian patients with pulmonary tuberculosis (TB) before and after antimycobacterial therapy, as well as in five Gambian and four Italian healthy immune control subjects. In untreated patients, most PPD-specific clones derived from either peripheral blood or pleural effusions showed a Th0 cytokine profile (production of both interferon [IFN]-gamma and interleukin [IL]-4/IL-5). After 6 mo of therapy and clinical healing, most PPD-specific clones showed a polarized Th1 profile (production of IFN-gamma but not IL-4/IL-5) in both Italian and Gambian patients. The Th1 polarization was less marked in Gambian than in Italian patients and failed to occur in another group of four Italian patients who experienced treatment failure. The cytokine profile observed after successful therapy in patients with TB was similar to that found in healthy control subjects. T-cell clones of undefined specificity generated from PPD-stimulated cultures showed a similar Th0/Th2 bias in Gambian individuals and Italian patients with treatment failure. The Th0/Th2-biased responses in Gambian patients before therapy could be modulated in vitro by IFN-alpha or IL-12, which induced a Th1 polarization of both PPD-specific and bystander T cells. Our data show that active TB associates with a predominant Th0 response to mycobacterial antigens that could play a role in the pathogenesis of the disease. Adjunctive immunotherapy using Th1-polarizing cytokines could increase host defense against mycobacteria and accelerate healing.

Autonomic control of heart rate variability in vasovagal syncope: a study of the nighttime period in 24-hour recordings.

Patients experiencing vasovagal syncope have been claimed to show reduced vagal tone over 24-hour electrocardiography recordings. Assessment of sympathovagal balance in the absence of external stimuli, i.e., nighttime electrocardiography monitoring, might help to clarify if increased sympathetic activity is present in these patients. Heart rate variability was examined at nighttime in 40 patients with recurrent episodes of vasovagal syncope within the last 2 years (22 men; mean age, 37 years) and 20 comparable healthy volunteers. Time domain parameters (pNN50 [proportion of successive RR intervals difference >50 ms in %] and rMSSD [root-mean-square successive difference of RR intervals in ms]), indexes of vagal tone, and frequency domain parameters, expressing the overall heart rate variability, vagal (high frequency [HF]) and sympathetic (low frequency [LF]) activity, and autonomic balance (LF/HF ratio) were compared between groups by Mann-Whitney test. Significant (p<0.05) reduction of heart rate variability and vagal tone (pNN50 and rMSSD) were found for patients with vasovagal syncope, together with increased sympathetic activity (increased LF/HF ratio). These findings could open new insights in the pathogenesis of vasovagal syncope because of the shift of the autonomic balance toward sympathetic activation near the syncopal episode.

Age-related changes of cardiac parasympathetic modulation after vasovagal syncope.

The time-domain analysis of 24-hour electrocardiographic recordings showed that vagal modulation of heart rate is reduced within 48 hours from vasovagal syncope. However, patients with recent vasovagal syncope can be differentiated from healthy subjects only up to the age of 40 years with this analysis, because this parasympathetic modulation physiologically decreases with increasing age.

Vagal control of heart rate variability in vasovagal syncope: studies based on 24-h electrocardiogram recordings.

The autonomic nervous system has an important role in the pathophysiology of vasovagal syncope. The purpose of this investigation was to evaluate to what extent the autonomic system is involved in the mechanism of fainting and to characterize the profile of heart rate variability of individuals who are prone to undergo a critical event. Thirty patients (mean age 41 years) with vasovagal syncope and 15 comparable controls were monitored by 24-h electrocardiography. Heart rate variability was analysed over the whole 24 h and during the daytime and night-time using time domain parameters (average of heart periods, RR; standard deviation of heart periods, SDNN; standard deviation of the average of RR intervals over all the 5-min segments of the entire recording, SDANN; percentage of the total number of all RR intervals of pairs of adjacent RR intervals differing more than 50 ms over the entire recording, pNN50; the square root of the sum of the square of differences between adjacent RR intervals, rMSSD), as indicated by the Task Force for Clinical Use of Standard Measurements of Heart Rate Variability. These parameters explore the influence of the autonomic nervous system on sinus node function and provide information about the vagal control to the heart. Among these parameters, pNN50 and rMSSD were significantly reduced in individuals with vasovagal syncope when compared with controls, over each time period considered. The two parameters are related to high-frequency oscillations in the frequency domain and to the vagal influence of the heart. These results indicate that the vagal tone to the heart is altered in subjects who suffer from vasovagal syncope. The results of this study provide an insight into the pathophysiological mechanism of fainting and may offer another means of evaluating patients with syncope.

The expression of alpha v, alpha 5, beta 1, and beta 3 integrin chains on ejaculated human spermatozoa varies with their functional state.

Evidence has been presented suggesting the involvement of integrins and their ligands in mammalian fertilization. In this study we asked whether the alpha 5, alpha v, beta 1 and beta 3 integrin chains, which form receptors for fibronectin and vitronectin, are present on human spermatozoa. Fresh ejaculate spermatozoa and capacitated spermatozoa, before and after a calcium ionophore (A23187)-induced acrosome reaction, were either fixed and their reaction with anti-integrin monoclonal antibodies detected by immunoperoxidase staining or studied without fixation, using cytofluorimetric scanning. Expression of specific integrin chains varied with the functional state of spermatozoa. The alpha 5 chain was not detected on fresh living spermatozoa, but was present on capacitated spermatozoa, whether fixed or living. The pattern of beta 1 expression on living spermatozoa paralleled that of alpha 5. No further increase in the expression of either alpha 5 or beta 1 was observed following an ionophore-promoted acrosome reaction. In contrast, alpha v was detected on neither fresh, living ejaculate spermatozoa, nor following capacitation (< 10% reactive). The percentage of alpha v positive cells increased substantially following ionophore exposure. Expression of beta 3 was similar to alpha v, and the percentage of cells displaying beta 3 correlated with the proportion of spermatozoa that had undergone an acrosome reaction, following ionophore exposure. These results indicate that the expression of integrins on spermatozoa is dynamic, varying with their functional state and that integrin receptors for fibronectin (alpha 5 beta 1) become apparent on the spermatozoan surface during capacitation and vitronectin (alpha v beta 3) following the acrosome reaction.

Heart rate and blood pressure variability in orthostatic syncope.

The pathogenetic role of autonomic nervous system in the neurally mediated orthostatic vasodepressive syncope is unclear. upright tilt was used to assess the characteristics of autonomic tone during orthostatic stress. We studied 18 patients (mean age 26 +/- 5 years) suffering from vasodepressive orthostatic syncope and with positive response to a 30-minute 60 degrees upright tilt and a comparable control group with a negative response to the upright tilt test. Blood pressure and heart rate (RR Interval) were measured beat-by-beat; ECG, systolic (SAP) and diastolic arterial pressure (DAP) and respiration trace were recorded for spectral analysis. The most important result of the work is a different pattern of the parameters evaluated, between fainters and controls, in the last period of tilt test, just before the syncope, and in the fainters group between the first (at the beginning) and the last period (just before syncope) of tilting. Baseline heart rate, arterial pressure and spectral indices were similar and increased with tilting in both groups (Low Frequency: LF; High Frequency: HF; LF/HF ratio). Just before the syncope, we observed in fainters group a decrease of heart rate, blood pressure, LF-RR, LF-DAP, LF-SAP, LF/HF -RR, and an increase of HF-RR and of total power where compared to in the same subjects in the first period of tilt and in front of controls in the same period of tilt. The novel aspect of the work, regarding the autonomic control of heart rate and arterial pressure, expressed by spectral fluctuations and by haemodinamic parameters, is consistent with a reduced sympathetic reserve in the immediate pre-syncopal period.

Randomised comparison of subcutaneous heparin, intravenous heparin, and aspirin in unstable angina. Studio Epoorine Sottocutanea nell'Angina Instobile (SESAIR) Refrattorie Group.

Intravenous heparin has been used in the control of myocardial ischaemia in patients with unstable angina. We set out to assess the efficacy of subcutaneous heparin in reducing myocardial ischaemia in patients with unstable angina. 343 of 399 patients with unstable angina were monitored for 24 h and 108 were refractory to conventional antianginal treatment and were entered into a randomised multicentre trial. 37 patients were assigned to heparin infusion (partial thromboplastin time 1.5-2 times baseline), 35 to subcutaneous heparin (adjusted dose with partial thromboplastin time 1.5-2 times baseline), and 36 to aspirin (325 mg daily). All had additional conventional antianginal therapy. After the run-in patients were monitored for 3 days. The primary endpoint was reduced myocardial ischaemia assessed by the number of anginal attacks, silent ischaemic episodes, and duration of ischaemia per day. At 1 week and 1 month we accounted for anginal attacks and other clinical events (myocardial infarction, revascularisation procedures, and death). Aspirin did not significantly affect the incidence of myocardial ischaemia. On the first 3 days, infused and subcutaneous heparin significantly decreased the frequency of angina (on average by 91% and 86%, respectively), episodes of silent ischaemia (by 56% and 46%), and the overall duration of ischaemia (66% and 61%) versus run-in day and aspirin (p < 0.001 for all variables). The favourable effects of heparin therapy remained evident during follow-up. Only minor bleeding complications occurred. Subcutaneous heparin is effective in the control of myocardial ischaemia in patients with unstable angina.

Twenty-four-hour blood pressure changes in young Somalian blacks after migration to Italy.

Blood pressure changes induced by migration from Somalia to Italy were studied in 25 normotensive clinical healthy blacks (aged 29 +/- 6 years) who had immigrated from Mogadishu to Florence. Basal and 24-h ambulatory blood pressure, venous compliance, and daily urinary electrolyte excretion were measured on arrival and 6 months later. After 6 months both basal pressure (P < .05 for systolic blood pressure, P < .01 for diastolic blood pressure) and 24-h blood pressure (P < .004 for systolic blood pressure, P < .01 for diastolic blood pressure) had significantly increased. Urinary sodium excretion had also increased (P < .001), whereas plasma renin activity was significantly reduced (P < .05). The ambulatory pressure increase was significantly related to the urinary sodium increase (r = 0.49; P < .01). At follow-up 8 of 25 blacks were hypertensive according to the WHO definition (basal diastolic blood pressure > 90 mm Hg). In conclusion, an increase in 24-h blood pressure is detectable after immigration and changes seems to be mainly related to higher sodium intake in the Western diet.

[Arterial hypertension in the black race]. / L'ipertensione arteriosa nella razza nera.

Hypertension represents a major health problem for black populations living in Western countries. In particular, blacks living in the United States have a three- to fivefold greater mortality from hypertensive disease than do whites. Better knowledge of the pathophysiology of hypertension in blacks can aid in the treatment of recently urbanized black people coming to Italy from African countries. Hypertension occurs more frequently in blacks than in whites, due to increased volemia; this characteristic seems to be related to a genetically determined increase in sodium sensitivity. Environmental factors seem to play a relevant role. Several studies performed on blacks migrating from rural to urban areas both in Africa and the USA, have shown that urbanization is closely related to increased blood pressure. The occurrence of cardiac and cerebrovascular complications of hypertension also seems to be closely related to socioeconomic factors. In fact, recently immigrated black people often lack health care facilities and consequently have poor control of hypertension. The environmental factors could be overcome by implementing systems to improve health care facilities, in particular blood pressure control, for recently urbanized blacks.

Beta-human chorionic gonadotropin and alpha-fetoprotein in central and peripheral venous blood of patients with testicular tumors.

From January 1989 to June 1991, 18 patients ranging in age from 19 to 41 (mean 34) years with testicular tumor were examined. 14 patients had seminoma (11 typical and 3 spermatocytic) and 4 patients had a mixed form (2 seminoma + embryonal tumor and 2 seminoma + teratocarcinoma). Serum levels of beta-human chorionic gonadotropin and alpha-fetoprotein from peripheral venous blood and from spermatic venous vessel were evaluated in every patient. All patients with seminoma and in a patient with mixed tumor (seminoma + embryonal tumor) the markers were regular. The increase of the markers was found in the peripheral and in spermatic blood of 3 patients (2 seminoma + embryonal carcinoma and 1 seminoma + teratocarcinoma). For these reasons the values of spermatic vessels are an important confirmation of the level of peripheral markers.

Sexual dysfunction after excision of the rectum.

From January 1986 up January 1988 a series of 18 patients--age average 49--were studied. All of them had undergone the amputation of the rectum for carcinoma with the Miles resection technique (15 p.), or for ulcerous rectumcolitis (3 p.). Six months after operation the patients were given a questionnaire in order to obtain information about their sexual activity. Exams on the liverkidney functioning, the hormone dosage (FSH, LH, prolactin, testosterone), penile Doppler flowmetry, and the sacral latency test were performed. The patients were also given a Jonas erectiometer to be used at home. The procedures followed have shown in most patients normal hormonal, vascular, and neurologic parameters, thus confirming the absence of relevant erectile deficits. Only one patient no longer had erections after the surgical intervention. It was reported a decrease and some sort of difficulty in the sexual intercourse owing to the presence of colostomy conditioning the physical and psychological relations with the partner. Spermatic fluid results altered after operation: absent in 8 cases, backwards in 3, diminished in 6, and normal in 4.