[Cat scratch disease and other human infections caused by Bartonella species]. / Maladie des griffes du chat et autres bartonelloses.

The different Bartonella species can cause various human infections such as cat scratch disease, chronic bacteremia (homeless patient with nonspecific symptom), endocarditis, bacillary angiomatosis, peliosis, and Carrion's disease. Diagnostic approaches include serology, culture and molecular approaches. PCR is especially useful on lymph nodes biopsies from patients with cat-scratch disease and on valvular samples taken from culture-negative endocarditis. Serology exhibits a very high sensitivity in the latter situation. The treatment should be chosen according to the clinical presentation.

[Animal bites and infection]. / Morsures d'animaux et risque infectieux.

Animal bites, mostly dog bites, often require an emergency department visit, but are often mistakenly considered innocuous. Indeed, bite wounds can lead to an handicap as well as become infected, mostly with the oral flora of the biting animal (Pasteurella, Capnocytophaga, Eikennella, streptococci, staphylococci and anaerobic bacteria). Bites can also cause other infections like tetanus, rabies, cat scratch disease, tularemia, leptospirosis, rat-bite fever and plague. The management of bite wounds includes prophylactic (antimicrobial prophylaxis, tetanus and rabies immunization) and therapeutic aspects (local treatment and antimicrobial therapy).

[Rickettsiosis: a clinical approach]. / Approche clinique des rickettsioses.

Rickettsiosis are zoonotic diseases transmitted to humans by arthropods. Prevalence of imported disease increases in parallel to the frequency of international travel. Clinical presentation is characterised by fever, headache and rash. Delay in the initiation of an antibiotic treatment efficient on Rickettsia spp. may have fatal impact on evolution. Serology is the more widely used diagnostic test. However, it only provides retrospective diagnosis. Polymerase chain reaction (PCR) and immunohistochemistry may provide early diagnosis. Doxycyclin is the first-line treatment and should be given empirically as soon as a rickettsial disease is suspected.

Changes in central monoaminergic function during chronic treatment with clonidine in the spontaneously hypertensive rat.

Clonidine was administered intravenously via osmotic minipumps at doses of 0.1 and 0.5 mg X kg-1 X 24 h-1. Both doses lowered blood pressure to the same degree by the third day of treatment. Only the higher dose significantly lowered heart rate. There was no tolerance to these cardiovascular effects which were maintained up to the seventh day of clonidine infusion. The only clonidine-induced change in central monoaminergic function was an increase in the adrenaline levels in the hindbrain. No other changes in central monoaminergic function in either cortex or hindbrain were detected at the level of the enzymes (tyrosine hydroxylase) of the neurotransmitters (noradrenaline, dopamine) or of the adrenoceptors [( 3H]clonidine binding). Our results suggest that clonidine lowers blood pressure via inhibition of release of hindbrain adrenaline.

Attenuation of the baroreceptor reflex by general anesthetic agents in the normotensive rat.

We have investigated the effects of urethane, a urethane + allobarbital mixture, alpha-chloralose and sodium pentobarbital on baroreceptor reflex function in the normotensive rat. Results were compared to those obtained in the conscious rat. Baroreceptor reflex function was evaluated from the fall in heart rate which accompanied the rise in diastolic arterial pressure following intravenous administration of phenylephrine. All four anesthetic agents attenuated reflex function as shown by a decrease in the bradycardiac response. There was a four to five-fold attenuation with urethane and urethane + allobarbital and a two- to three-fold attenuation with alpha-chloralose and sodium pentobarbital.

Chronic clonidine treatment and its withdrawal: effects on blood pressure and catecholamine synthesizing enzymes in brain-stem nuclei.

We have studied the effects of withdrawal from chronic clonidine treatment in the adult male spontaneously hypertensive rat (SHR). SHR received clonidine, 0.1 mg X kg-1 X day-1 i.v. for 10 days. Clonidine was delivered via osmotic minipumps. After 7 days of treatment there was a 16.5 +/- 2.5 mm Hg fall in mean arterial pressure. This was accompanied by a decrease in the dopamine-beta-hydroxylase and phenylethanolamine-N-methyl transferase activities of the A1/C1 region. Withdrawal from clonidine was characterized by tachycardia and an increase in mean arterial pressure and heart rate lability. Phenylethanolamine-N-methyl transferase of the the dopamine-beta-hydroxylase activity remained diminished. The dopamine-beta-hydroxylase activity of the A2/C2 region was also diminished during withdrawal. We suggest that the blood pressure lowering effect of clonidine is accompanied by a decreased capacity to synthesize adrenaline in the A1/C1 region where adrenaline could mediate a pressor effect. Increased blood pressure lability during withdrawal is accompanied by a restoration of synthesis of adrenaline in the A1/C1 region. There is also a decrease in the capacity of synthesis of noradrenaline in the A2/C2 region where adrenaline may mediate a vasodepressor effect.

Influence of streptozotocin-induced diabetes on blood pressure and on renin formation and release.

I.v. injection of 40 mg/kg or 65 mg/kg streptozotocin reliably induced diabetes in female Sprague-Dawley rats, but failed to induced hypertension within the following 42 days. In most animals injected with the higher dose and in some animals injected with the lower dose the tail blood flow was permanently impaired so that no blood pressure signals could be obtained by tail plethysmography. This phenomenon occurred also when the drug was injected into the jugular vein and thus was not due to a local effect of streptozotocin. 15 days after 65 mg/kg streptozotocin, the mean arterial pressure of the rats was similar to that of controls, when measured inthe awake state (carotid cannula) or under ether anaesthesia. 42 days after streptozotocin, under pentobarbital anaesthesia, the blood pressure was again normal in the animals given 40 mg/kg of the drug and depressed in the animals given 65 mg/kg of the drug 42 days previously. The increase of blood pressure induced by 1 microgram/kg (-)-noradrenaline i.v. was similar in the latter group of animals and in controls. The renal cortical renin concentration was much lower than in controls 42 days after either dose of streptozotocin, while the plasma renin activity was normal (40 mg/kg) or increased 65 mg/kg). The low renal renin content may have been due to the diabetic state, rather than to the drug itself. Adrenal medullary dopamine-beta-hydroxylase activity was increased 42 days after the higher dose of streptozotocin.

Effect of prolonged clonidine treatment and its withdrawal on noradrenaline turnover in the cerebral cortex and medulla oblongata of the spontaneously hypertensive rat.

We have investigated the effect of prolonged treatment with clonidine (delivered intravenously via osmotic minipumps, 0.5 mg . kg-1 X 24 h-1 for 10 days) and of withdrawal of this treatment on ingestive behaviour and on the cerebral turnover of noradrenaline in the adult spontaneously hypertensive rat (SHR). Clonidine amplified the fall in food and water intakes induced by minipump implantation. Ingestive behaviour returned to normal by the 4th to the 5th day in controls and by the 7th to the 8th day in clonidine-treated SHR. Clonidine withdrawal produced an increase in water intake above pre-implantation values. Body weight fell during clonidine treatment, then recovered slightly during withdrawal. After 5 days' treatment total DOPEG levels (an index of noradrenaline turnover) were reduced in cerebral cortex and medulla oblongata. The noradrenaline metabolite levels increased following withdrawal of drug treatment, the increase being more marked and faster in onset in cerebral cortex than in medulla oblongata. Thus prolonged treatment with clonidine decreases noradrenaline turnover and withdrawal of such treatment increases turnover.

Alpha-1 and alpha-2 adrenoceptor agonists induce vasoconstriction of the normotensive rat caudal artery in vitro by stimulation of a heterogeneous population of alpha-1 adrenoceptors.

Although alpha-2 adrenoceptor agonists rapidly induce arterial vasoconstriction in vivo, such responses have proven difficult to obtain in vitro. We have investigated the vasoconstrictor effects of various alpha-1 and alpha-2 adrenoceptor agonists in the perfused superfused caudal artery of the normotensive rat. Intrinsic activities were; methoxamine; 1, phenylephrine; 0.94, noradrenaline; 0.93, guanfacine; 0.88, clonidine; 0.47, UK 14,304 [5-bromo-6-(2-imidazoline-2-ylamino)-quinoxaline tartrate]: 0.10, azepexole; 0. Antagonism by the selective alpha-1 agent, prazosin of the vasoconstrictor responses provoked by methoxamine, guanfacine or clonidine, showed a high affinity with--log KB values in the range of 8.5 to 9.4. There were no significant differences between the KB values obtained with the three agonists. Antagonism by the selective alpha-2 antagonist, yohimbine showed a low affinity with KB values between 6.7 to 7.6 for the three agonists. The calcium entry blocker, nicardipine, antagonized responses to clonidine at nanomolar concentrations and those to phenylephrine at micromolar concentrations. We conclude that vasoconstrictor responses in this isolated tail artery preparation are primarily mediated via an alpha adrenoceptor which can be classified, on the basis of the results with specific antagonists, as being of the alpha-1 type. The results obtained with nicardipine suggest that the population of alpha adrenoceptors is not, however, homogeneous.

Greater vasodepressor sensitivity to nicardipine in spontaneously hypertensive rats (SHR) compared to normotensive rats.

Differences in the degree of attenuation by the calcium entry blocker, nicardipine, of the pressor responses to alpha-1 (phenylephrine) and alpha-2 (UK 14.304) adrenoceptor agonists was investigated in pentobarbital-anesthetized, normotensive Sprague-Dawley (SD) or Wistar Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR), treated with the ganglionic blocking agent, pentolinium. Following administration of the ganglionic blocking agent, pentolinium, nicardipine produced a significant fall in blood pressure in SHR but not in SD or WKY rats. Nicardipine had no effect on the basal blood pressure of pithed SHR. In rats treated with the ganglionic blocking agent, pentolinium, nicardipine produced parallel shifts to the right in the dose-response curves for phenylephrine but had no effect on maximal responses to phenylephrine. The decrease in the ED50 of phenylephrine was greater in the SHR than in normotensive rats. Nicardipine produced a decrease in both the ED50 and the maximal response to the alpha-2 adrenoceptor agonist, UK 14.304. The decrease in the maximal response was greater in SHR than in WKY normotensive rats but the change in ED50 for UK 14.304 was greater in WKY than in SHR. SD normotensive rats gave intermediate results. We conclude that the inhibition of alpha-adrenoceptor-mediated pressor responses by nicardipine is generally more pronounced in SHR than in normotensive rats. This suggests that hypertension may be accompanied by an increase in the sensitivity of peripheral resistance beds to calcium entry blockers.

Cyclohexamide and renin release following renal artery constriction.

Renal artery constriction in the uninephrectomized conscious rat produced "renin release": i.e. an increase in plasma renin level and a decrease in renal cortex renin level, and an increase in mean arterial pressure. A high dose (4 mg.kg-1) of the protein synthesis inhibitor, cyclohexamide, halved the rise in plasma renin level (with no change in renal cortex renin level and a fall in mean arterial pressure). We suggest that the increase in plasma renin level following renal artery constriction depends on (a) release from preformed renin stores and (b) de novo renin synthesis.

Effect of acute administration of prazosin on blood pressure, heart rate and plasma renin level in the conscious normotensive rat.

This study investigated whether the specific alpha-antagonist, prazosin, stimulated basal plasma renin levels and heart rate. Furthermore the beta-adrenergic nervous system was also investigated to ascertain whether it was involved in this effect. Prazosin (0.1 or 1 mg/kg) was injected subcutaneously (s.c.) to conscious normotensive rats, either alone or in combination with the beta-adrenoceptor antagonist, DL-propranolol (1 or 3 mg/kg). Rats bore chronically implanted dorsal aorta cannula for measurement of blood pressure and heart rate and blood sampling for renin determinations. Acute administration of prazosin (1 mg/kg, s.c.) produced a fall in mean arterial pressure accompanied by renin release and tachycardia. A tenfold lower dose of prazosin did not alter blood pressure or heart rate but did stimulate renin release. Acute administration of DL-propranolol, (1 or 3 mg/kg, s.c.) produced falls in blood pressure and heart rate but did not affect plasma renin level. Combinations of prazosin with propranolol gave falls in blood pressure similar to those predicted on the basis of a simple addition of the effects of the two drugs given separately. Prazosin-induced tachycardia and renin release were attenuated by propranolol. It appears that prazosin produces renin release and tachycardia via stimulation of the beta-adrenergic adrenoceptor.

Effect of chronic clonidine treatment and its abrupt cessation on mean blood pressure of rats with a normal or an elevated blood pressure.

1. Clonidine (6 mg of base/l of water) was given as drinking fluid to normotensive rats or rats with established or early hypertension. 2. Spontaneous hypertensive rats (6 months old: average dose of clonidine, 0.6 mg 24 h-1 kg-1) showed a sustained fall in blood pressure over 3 weeks. 3. The same clonidine solution given for 6 weeks to two-kidney Goldblatt rats with early-stage hypertension (average dose of clonidine: 1 mg 24 h-1 kg-1) or spontaneously hypertensive rats (clonidine dose: 1 mg) induced a fall in mean blood pressure, but no change in normotensive rats. 4. Replacement of clonidine by water induced hypertension and lability which led to death in hypertensive but not in normotensive rats.

Noradrenaline inhibits vasoconstriction induced by electrical stimulation.

Exposure of the isolated rat tail artery to exogenous noradrenaline inhibited vasoconstriction induced by electrical field stimulation. Phenylephrine produced brief inhibition; guanfacine potentiated electrical stimulation. Sympathetic neurotransmission may be blunted by brief increases in circulating noradrenaline levels.

The role of the renin-angiotensin system in normotensive and hypertensive rats with varying renin status.

We have investigated the relationship between the acute blood pressure lowering effect of captopril and renin status. Differences in renin status were induced by unilateral artery clipping combined with unilateral or bilateral nephrectomy in rats. The blood pressure lowering effect of captopril correlated very closely with plasma or aortic renin across a very wide range of renin levels.

Changes in the vascular reactivity of the isolated tail arteries of spontaneous and renovascular hypertensive rats to endogenous and exogenous noradrenaline.

We have investigated the changes in the responses to noradrenaline of isolated tail arteries of spontaneously hypertensive (SHR) and renovascular hypertensive rats (Wistar-Kyoto: two-kidney, one-clip model, WKY:2K1C) compared with normotensive (Wistar-Kyoto, WKY) rats. Renovascular hypertension was induced by 4 weeks' unilateral renal artery clipping. Arteries were vasoconstricted with exogenous noradrenaline, electrical field stimulation or high potassium. The effects of the latter two stimuli were abolished by reserpine and so were presumably dependent on the presence of endogenous noradrenaline. In the SHR the maximal vasoconstriction produced by all three stimuli was greater than in WKY. Dose-response curves were steeper and there was no change in threshold. Vascular mass was greater. We interpret these results as showing an increase in vascular reactivity in the SHR caused by structural adaptation. The WKY:2K1C responses to noradrenaline could also be explained in terms of structural adaptation but there was no increase in vascular mass. Sensitivity to potassium and electrical stimulation was decreased, suggesting a defect in vascular neurotransmission. This was supported by the observations of a decreased arterial noradrenaline content and of decreased sensitivity to cocaine.