A bereavement support group intervention is longitudinally associated with salutary effects on the CD4 cell count and number of physician visits.

A randomized, controlled, clinical trial was conducted to examine the impact of a semistructured, 10-week, once weekly, 90-min/session bereavement support group intervention on immunological, neuroendocrine, and clinical health status in human immunodeficiency virus type 1-seropositive (HIV-1+) and HIV-1-seronegative (HIV-1-) homosexual men, compared to a standard of care control condition. A total of 119 homosexual men (74 HIV-1+ and 45 HIV-1-) were assessed at baseline, 10 weeks, and 6 months follow-up. At the 6-month follow-up assessment, the intervention groups exhibited significant beneficial effects compared to controls on changes in CD4 cell, total T-lymphocyte, and total lymphocyte counts, when baseline levels, antiretroviral medication use, CDC stage of disease, and other potentially confounding factors were accounted for. There was no statistically significant effect on the CD4/CD8 ratio or on the CD8 cell count. The effect on CD4 cell count was associated with group attendance and with changes in plasma cortisol level. Plasma cortisol levels decreased significantly among intervention subjects, compared to controls. A significantly reduced number of health care visits over the 6-month follow-up period among the intervention subjects supported the clinical relevance of the immunological changes observed for both HIV-1+ and HIV-1- individuals. These results indicate that behavioral interventions may have salutary immunological and clinical health effects following bereavement among HIV-1-infected individuals. The effect in HIV-1- individuals suggests that this bereavement support group intervention might have similar salutary effects in the general population. Potential effects of such interventions on clinical HIV disease progression are of interest and should be studied.

CO2 anesthesia facilitates a serum antibody response to orally-administered antigens.

Under most experimental circumstances, mice fed a protein antigen produce a smaller serum antibody response than the response elicited in mice that are parenterally immunized with that same antigen. In our experiments, mice fed keyhole limpet hemocyanin or herpes simplex virus type 1 had low, if any, serum IgG antibody responses regardless of whether antigen consumption was voluntary (in drinking fluids) or involuntary (force-fed by pipette). However, when force-feeding occurred during CO2 anesthesia, mice produced significantly higher serum antibody responses, which were comparable to those elicited in mice injected intraperitoneally with the same antigen. Although its mechanism of action is unclear, this potentiating effect does not appear to be mediated by possible CO2-mediated entry of the antigens into the respiratory tract, since mice fed antigen immediately before CO2 anesthesia also had a substantial antibody response.

A non-lectin-like mechanism by which Fusobacterium nucleatum 10953 adheres to and activates human lymphocytes.

Most (approximately 80%) strains of Fusobacterium nucleatum adhere to human erythrocytes in a lectin-like manner that is strongly inhibited by N-acetyl-D-galactosamine (GalNAc). In this study, we investigated the capacity of F. nucleatum 10953, a strain that is weakly inhibited by GalNAc, to adhere to and activate human lymphocytes in vitro. Experiments using [3H]-labeled bacteria and scanning electron microscopy clearly showed that 10953 adhered to lymphocytes and that adherence was blocked by L-arginine+GalNAc greater than L-arginine much greater than GalNAc. Adherence was Ca(2+)-dependent, inhibited by pretreatment of the bacteria with proteases or heat, and unaffected by paraformaldehyde fixation of the bacteria. Strain 10953 induced lymphocyte mitogenesis that was blocked by L-arginine but not by GalNAc. These results suggest that certain strains of F. nucleatum, such as 10953, express a distinct, non-lectin-like mechanism by which they adhere to and activate lymphocytes. Activation of lymphocytes may be an important mechanism in the pathogenesis of periodontal diseases associated with these bacteria.

Interaction of Fusobacterium nucleatum 191 with human peripheral blood lymphocytes.

Fusobacterium nucleatum is frequently isolated in high numbers from the subgingival plaque of patients with periodontal diseases. Adherence of these bacteria to several host tissues is lectin-like in that it is inhibited by galactose, lactose, and N-acetyl-galactosamine. Since F. nucleatum has the capacity to activate human peripheral blood lymphocytes, the purpose of this study was to determine whether F. nucleatum adheres to lymphocytes and, if so, to determine whether lectin-like interactions facilitate lymphocyte activation. Adherence of F. nucleatum strain 191 to lymphocytes was confirmed by agglutination assays, scanning electron microscopy, and by using fluorescein- or [3H]-labeled bacteria. Saturation of adherence was reached at about 35 bacteria per lymphocyte. F. nucleatum adhered to greater than 90% of the lymphocytes, and adhered in higher numbers to B cell-enriched subpopulations than to T cell-enriched subpopulations. Adherence was inhibited by N-acetyl-galactosamine, lactose greater than galactose, alpha- and beta-methyl galactoside, but not by 100 mM glucose, mannose, N-acetyl-glucosamine, or other sugars tested. Lymphocytes underwent mitogenesis when preincubated with bacteria and washed to remove weakly adherent and non-adherent bacteria. Mitogenesis induced by low concentrations of F. nucleatum was reduced, but not completely eliminated, by N-acetyl-galactosamine. However, N-acetyl-galactosamine had no effect on mitogenesis induced by preincubation with high concentrations of bacteria. These results suggest that adherence of F. nucleatum facilitates activation of lymphocytes, particularly at low concentrations of bacteria.

Antihypertensive effect of interleukin-2.

Recent reports indicate that cyclooxygenase inhibitors such as aspirin may facilitate the release of interleukin-2 from thymic T cells. We have previously reported that aspirin has antihypertensive effects in the standard animal model of essential hypertension, the spontaneously hypertensive rat (SHR). Because the SHR has been reported to be deficient in T cells, it was of interest to determine whether the course of hypertension in this model could be altered by interleukin-2, the T cell growth factor. A single bolus of interleukin-2 (5,000 units/kg s.c.) prevented the increase of blood pressure in the young SHR and lowered pressure to normotensive levels in the well-established hypertensive adult SHR. In the latter, the effects of a single dose have been found to persist for at least 6 months with no toxic or untoward effects apparent. Blood pressure in Goldblatt, single-kidney wistar-kyoto rats, a model of renal hypertension, was not affected by interleukin-2.

In vitro uterine response to tetramethylpyrazine, the active constituent of chung chong (a traditional Chinese medicine).

Tetramethylpyrazine is extracted from Rhizoma ligustici wallichii, an herb used in the Chinese medicine Chung Chong. Both herb and extract have been used in the treatment of anginal pain and stroke. Animal studies in the West have shown that tetramethylpyrazine improves coronary blood flow, is short acting, and has a low toxicity. There are no clinical or animal studies on the uterine effects of tetramethylpyrazine. We present results of a preliminary study with isolated uterine strips from rats. We found that tetramethylpyrazine, in a dose-dependent manner (0.6 to 20 micrograms/ml), reduced uterine diastolic tone and inhibited the response to oxytocin (0.02 to 0.32 micrograms/ml). Higher concentrations of tetramethylpyrazine were needed to block the uterine responses to prostaglandin E2 (0.01 to 0.1 microgram/ml). On the basis of clinical and folk experience in the Far East, tetramethylpyrazine appears to have fewer systemic effects in human beings than have the beta-adrenergic agonists or calcium channel blockers. We suggest that studies in the whole animal and in the clinic might provide reasons to use tetramethylpyrazine to reduce uterine contractions and tone in pregnant women at term.

Aluminum in the organs and diet of ageing C57BL/6J mice.

Total aluminum concentrations increased with ageing in the liver and kidney of male C57BL/6J mice, remained unchanged in brain and heart, and decreased with ageing in femur and lung for mice ranging in age from 56 to 1186 days. Ligating one kidney did not significantly increase aluminum concentrations in the various organs. Feeding 1 X 10(-2) M aluminum chloride (270 ppm Al) in the drinking water beginning at 604 days of age decreased the average life span by 6.7%. We conclude that very little aluminum accumulation occurs with ageing in the organs tested in this study, in spite of a high dietary intake. Other organs might show a change. Only one aluminum concentration was used in this study which accelerated the rate of ageing as indicated by a change in the survival curve. The effect of higher or lower aluminum concentrations remains to be seen.

Age and the antihypertensive effect of aspirin in rats.

1. We previously showed that chronic exposure to aspirin (100 mg kg-1 daily, by mouth) is effective in preventing the onset of hypertension in young (28-84 day old) spontaneously hypertensive rats (SHRs). This is contrary to what others have reported using older SHRs. 2. Renal prostaglandin F2 alpha was also reduced in young SHRs and Wistar-Okamoto strain rats (WKYs) exposed to aspirin. 3. In the present study we extended the period of aspirin treatment in young rats to beyond 84 days of age. We found that aspirin lost its antihypertensive effect in SHR and WKY rats at 110 +/- 7 days of age regardless of whether the exposure to aspirin had begun at age 28, 49 or 87 days. 4. We conclude that the loss of antihypertensive effect of aspirin in the SHR and in older WKY rats, is determined by some factor(s) probably not related to prostaglandin F2 alpha, which reaches full expression in the 110 +/- 7 day old rat, or is fully dissipated at this age. 5. The anti-PGF2 alpha activity of aspirin in the SHR and WKY rat was short-lived and apparently unrelated in time to the antihypertensive effect of aspirin.

Sympathetic, muscarinic vasodilation in cranial vessels of the cat.

Pressor responses evoked by stimulation of the preganglionic sympathetic trunk of the feline superior cervical ganglion have been recorded in vivo from the vascular bed perfused by one external carotid and the vertebral artery. When vasoconstrictor activity is blocked and potential vasodilator activity enhanced by close, intracarotid injection of guanethidine and prostaglandin F2 alpha respectively, stimulation evokes a weak pressor response followed, on cessation of stimulation, by a prolonged vasodilation lasting for 6-8 min. The magnitude and duration of the poststimulation vasodilation was reduced significantly by atropine. Due to the prolonged nature of the vasodilation, it is unlikely that a sympathetic cholinergic vasodilation in the classical sense is involved.

Separation of antihypertensive from ganglioplegic effects of felodipine in the cat.

The effects of felodipine on sympathetic ganglionic transmission and on the effector responses of two muscle models were studied. In anesthetized cats we established what injected dose and plasma levels of this selectively vasodilating dihydropyridine were necessary for the neural and for the primary hypotensive effects on arterial blood pressure in vivo. Felodipine in cats reduced mean arterial pressure at a dose of 0.010 mumol/kg i.v., corresponding to a plasma concentration of 10 nmol/L. A 15-25-fold higher dose, or plasma concentration, was required to produce a significant reduction in the amplitude of the sympathetic postganglionic action potential (PAP). The latencies of the PAPs remained constant. Felodipine in vitro did not attenuate the neurogenic response of the nictitating membrane. However, the spontaneous activity, as well as the neurogenic response of the portal vein, was inhibited by felodipine in nanomolar concentrations. Felodipine at the highest dose caused a small but significant attenuation of the postganglionic nictitating membrane response in vivo. This reduction was of insufficient magnitude to account alone for the diminution of the response to preganglionic stimulation. We conclude that felodipine in low concentrations reduces blood pressure by a direct relaxation of vascular smooth muscle, while, in addition, at high concentrations a partial ganglionic blockade may be induced.

Inhibition by metoprolol of the antihypertensive effect of aspirin in young rats.

A group of 21-day-old, spontaneous hypertensive rats (SHR) received either aspirin (75-100 mg/kg), metoprolol (1.0-1.5 mg/kg) or both in their drinking water for 56 days. Controls received plain water. Groups of normotensive Wistar-Kyoto rats (WKY) received the same drug treatment as did the SHR. Blood pressure, heart rate and body weight were determined weekly, and water consumption was monitored on a daily basis. Renal prostaglandin (PG) activities were determined in a separate group of rats at 7 and at 56 days on each protocol. Blood pressures in the SHRs remained in the range of the WKY during 56 days of treatment with aspirin or metoprolol, but increased to hypertensive levels after exposure to plain water. Blood pressures in the WKY receiving aspirin or metoprolol were also lower than those receiving plain water, but the antihypertensive effect was somewhat slower in onset. The antihypertensive effects of aspirin and of metoprolol were lost in the SHR but not in the WKY when both drugs were given simultaneously in the drinking water. In comparison to rats receiving plain water, renal PG activity (PGF1 alpha and PGF2 alpha) was lower in rats receiving aspirin, metoprolol or both together. The mechanism for the antihypertensive effect of aspirin in the young SHR may be related to a decline in renal PG content, or to the release of other hormones controlling water and electrolyte balance. Reports that the cyclooxygenase inhibitors, such as aspirin, can block the antihypertensive effect of the beta adrenoceptor antagonists is confirmed in chronic studies using the SHR model.(ABSTRACT TRUNCATED AT 250 WORDS)

Cephalic carotid pressure as a measure of transmission through cervical ganglion.

Cephalic or cranial pressure, i.e., pressure recorded craniad from the external carotid artery, was recorded in the cat during stimulation of the pre- and postganglionic trunks of the superior cervical ganglion (SCG) as was tension developed by the nictitating membrane under these situations. The influence of distension of the carotid sinus and of metoprolol on hemodynamic and tension responses was compared with control responses. Distension of the sinus with an indwelling balloon produced an increase of cephalic pressure evoked by stimulation of the SCG. Tension developed by the nictitating membrane was unaffected. Metoprolol reduced the increase in pressure resulting from stimulation of the preganglionic trunk of the SCG at 1.0 Hz but enhanced the pressure increase in the cranial circulation evoked by postganglionic stimulation of the SCG at 5.0 Hz. Action potentials, recorded postganglionically from the SCG, could be roughly grouped by height and latency into three populations. The height of the M3 population increased with distension of the carotid sinus. This study provides evidence that cephalic pressure can be used as a measure of the influence of various factors on the transmission of impulses through the SCG. This parameter appears to be a more sensitive measure of transmission than that of tension developed by the nictitating membrane. Distension of the carotid sinus is one factor that facilitates ganglionic transmission, whereas the beta-adrenoceptor antagonist metoprolol depresses it.

Sinusal afferents supplying superior cervical ganglion.

Sinusal distension can evoke activity in nerves supplying the superior cervical ganglion. These nerves, which have been shown to have little depressor influence, may carry an inhibitory input from the carotid sinus to the superior cervical ganglion (SCG). They have the morphological characteristics of the nerve of Hering and show cardiac pulse-related activity that may reach a maximum of 50 impulses/s during distension of the sinus. Electrical stimulation of the ascending preganglionic sympathetic trunk supplying the SCG may evoke discreet bursts of activity in these fibers, which do not summate with continued stimulation.

Carotid sinus distension and superior cervical ganglion transmission.

The functional relationship between sinusal distension and the sympathetic innervation of the feline carotid sinus was investigated by neurophysiological techniques. A balloon catheter was used to distend the sinus region while recording evoked postganglionic activity from the superior cervical ganglion. When the SCG was stimulated at 1.0 or 10.0/s, balloon inflation reduced postganglionic action potential height by 25-50% and increased ganglionic negativity. These effects were subsequently abolished by section of one of the remaining intact postganglionic trunks. This evidence suggests that a pressure-modulated reflex arc, similar to the intestinointestinal reflex, might exist between the carotid sinus and superior and cervical ganglion.

Enhanced depressor reflex by stimulation of superior cervical ganglion and by propranolol.

The systemic depressor reflex in cats evoked by inflation of an intrasinusal balloon is enhanced by stimulation of the superior cervical ganglion and by close infusion of 20 micrograms/ml/min of (d, l)propranolol.

Inferior cardiac nerve activity in the cat during superfusion of the vascularly isolated carotid sinus with propranolol.

1 Inferior cardiac nerve activity in 9 cats was in inverse relationship to the pressure maintained in the systemically isolated and perfused carotid sinus. 2 Perfusion with propranolol produced no change in this relationship at a concentration of 5.0 microgram/ml, but abolished it at 50.0 microgram/ml. 3 The results suggest that concentrations of propranolol which have been reported to enhance the sensitivity of the carotid sinus to pressure do not enhance one neurophysiological component of the reflex depressor response.

Inferior cardiac nerve activity in the cat during occlusion of the mesenteric artery.

A number of studies in this and other laboratories using hemodynamic and pharmacologic evidence have suggested that occlusion of the mesenteric artery evokes a pressor reflex initiated by mesenteric baroreceptors. To provide additional evidence in support of this hypothesis, neurophysiological recordings were made of inferior cardiac nerve activity during mesenteric artery occlusion (MAO). The results indicate that MAO enhances inferior cardiac nerve activity in the cat, providing that the carotid sinus nerves have been cut. Cutting of the mesenteric nerves further facilitates cardiac nerve activity and abolishes the response to mesenteric artery occlusion. The evidence suggests that MAO evokes a reflex sympathetic discharge which is subject to override by the carotid sinus depressor reflex. The afferent limb of the reflex is characterized by a tonic depressor outflow from the mesenteric pressure receptors.

A mechanism to explain the antihypertensive action of propranolol.

The present experiments were designed to measure the direct effects of propranolol on carotid sinus pressoreceptor nerve activity in the semi-isolated, superfused sinus of the cat. Propranolol (5 microgram/ml) significantly enhanced carotid sinus nerve activity at perfusion pressures of 100, 150 and 250 mm Hg. The enhancement was due primarily to the recruitment of new fibers. In similar preparations, perfused at constant flow, propranolol increased sinus resistance in parallel with the increase in sinus discharge. These effects were rapidly dissipated by rinsing with drug-free perfusion solution. The evidence suggests that propranolol may produce a change in either the elastic or autoregulatory modalities of sinus smooth muscle. This may produce a functional "resetting" of the sinus and provide a mechanism to explain the antihypertensive effect of propranolol.

Pharmacology of the hemodynamic and myocardial response to occlusion of the mesenteric artery in the cat.

Occlusion of the superior mesenteric artery in the cat produces increases in heart rate, systemic pressure, cardiac output and muscle blood flow. Total peripheral resistance is reduced and regional resistance in skin increased. Blockade of the right and left cardiac nerves with xylocaine lowered basal heart rate and reduced cardiac output. The increase in heart rate produced by occlusion of the artery (MAO) was prevented by blockade of the stellate ganglia and cardiac nerves. Propranolol lowered basal heart rate and cardiac output and subsequently blocked the increase in both parameters during MAO. The increase in muscle blood flow was also blocked resulting in an increase in total resistance. We conclude that, in the cat, MAO reflexly increases myocardial tone and enhances venous return from muscle, the latter by a reflex beta adrenergic vasodilation. Both factors provide for the increase in cardiac output. A reflex beta adrenergic vasodilation in muscle, evoked by vasoconstriction in the mesenteric bed, may contribute to survival in the hemorrhaged animals, since capillary exchange in muscle may be increased by this reflex and fluid shifted from the extra--to the intravascular compartment.