Does obestatin modulate the hypothalamic appetite-regulating network in peripubertal sheep?

The participation of peripheral peptides in the processes regulating the food intake (energy homeostasis) at the central nervous system level remains unclear. This study focuses on the role of obestatin in neuronal activity within the hypothalamic appetite-regulating network in ruminants. The animals (n = 28) were randomly divided into two groups. The sheep in the control group received intracerebroventricular infusions of the Ringer-Locke solution, and the sheep in obestatin group were infused with obestatin (diluted in the Ringer-Locke solution) at 25 µg per 120 µl/hr. The series of four 1-hr infusions on 3 consecutive days were performed, and immediately after the experiment, the sheep were decapitated. Selected brain regions were fixed in situ for further immunohistochemical analysis, while the remaining ones were frozen for real-time RT-qPCR analysis. Obestatin infusion elicited changes in the neuropeptide Y (NPY) neuronal network in the hypothalamus. The results obtained show that exogenous obestatin evoked an increase in npy and agrpmRNA expression in the mediobasal hypothalamus (MBH), while the immunoreactivity for NPY was decreased in the arcuate and periventricular nuclei. The increase in cart and pomcmRNA expression in the MBH was also observed. Moreover, increased levels of gpr39 receptor and npy receptor 1 mRNA expression were evident in obestatin-infused sheep. Based on these results, it can be concluded that obestatin plays a role in the modulation of appetite-regulating network at the central level in sheep. The results obtained suggest that the underlying mechanism may involve the modification of the activity of NPY/AgRP and CART/α-MSH neurons in the arcuate nucleus.

The intrapituitary endocrine events during maturation and timing of puberty in the female sheep.

The aim of this study was to determine the maturational activity of gonadotroph cells, the site of synthesis, storage and release of luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in Polish Merino female sheep born after the summer solstice. The actual time of puberty of these lambs was delayed until the following breeding season, when they were 14 months old. Changes were examined in 12 peripubertal (30-, 52-week-old) and pubertal (Days 15 and 17 of the second ovarian cycle) females. Histomorphological and functional changes in the gonadotroph population were assayed with hybridohistochemistry, immunohistochemistry, computer-assisted image analysis and radioimmunoassay. The percentage of the adenohypophyseal area (PAA) occupied by gonadotrophs containing LHbeta-mRNA was higher and the LH plasma concentration and pulse frequency were lower in the 52-week-old sheep in comparison with the 30-week-old sheep (P<0.05). The PAA occupied by immunoreactive (ir)-LHbeta-cells remained stable at the 30th and 52nd weeks of age and then increased at the pubertal follicular phase. The PAA occupied by ir-FSHbeta-cells was higher in the 52-week-old sheep compared with the 30-week-old sheep and then lower at the pubertal follicular phase (P<0.05). The PAA occupied by gonadotrophs containing LHbeta-mRNA or FSHbeta-mRNA was lower at the pubertal follicular phase in comparison with the 52nd week of age (P<0.05). In pubertal sheep, the PAA occupied by gonadotrophs containing LHbeta-mRNA or FSHbeta-mRNA was higher and the PAA occupied by ir-LHbeta or ir-FSHbeta-cells was lower at the preovulatory phase in comparison with the follicular phase of the cycle (P<0.05). In conclusion, the photoperiodic suspension of gonadotroph population's maturational functions has been observed at the level of LH storage and release but not at the level of LH synthesis during the expected time of puberty in female sheep of an aseasonal breed such as Merino. The findings show the heterogeneity in the patterns of LH and FSH post-transcriptional processing during the period of peripubertal/pubertal transition, explained by the different intrapituitary regulation at the level of post-transcriptional synthesis and storage rather, than at the level of release. Altogether, intrapituitary mechanisms of ovine maturation could have the histomorphological feature. Our observations prompt the hypothesis that the female lamb may be able to transduce changes in day length into the appropriate endocrine cues for sexual maturation after attainment by the pituitary gonadotroph population the full peripubertal efficiency, manifested by the sufficient storage of LH.

Comparison of atazanavir with lopinavir/ritonavir in patients with prior protease inhibitor failure: a randomized multinational trial.

OBJECTIVES: To compare change from baseline in HIV RNA and fasting low-density lipoprotein (LDL) cholesterol levels in protease inhibitor (PI)-experienced patients receiving unboosted atazanavir 400 mg once daily versus lopinavir 400 mg boosted with ritonavir 100 mg twice daily, with two nucleoside reverse transcriptase inhibitors (NRTIs). Secondary objectives included virologic response, CD4 cell count changes, other lipid changes, safety, and tolerability. METHODS: Randomized, open-label, multinational, 48-week study in patients with one PI-regimen failure, HIV RNA > or = 1000 copies/mL, and CD4 count > or = 50 cells/mm3. RESULTS: Three hundred patients were randomized; 290 treated (144 atazanavir, 146 lopinavir/ritonavir). Lopinavir/ritonavir resulted in a significantly greater reduction in HIV RNA than unboosted atazanavir (-2.02 vs -1.59 log10 copies/mL, p < 0.001) at week 48. Secondary efficacy endpoints also favored lopinavir/ritonavir; the differences in efficacy between regimens were also observed in secondary analyses comparing those subjects who were susceptible and those subjects who were resistant to their respective PIs at baseline. However, both regimens were equally effective in subjects who had no baseline NRTI mutations. From baseline to week 48, atazanavir resulted in either no change or decreases in fasting LDL cholesterol, total cholesterol, and fasting triglycerides (-6%, -2%, and +1%), whereas lopinavir/ritonavir resulted in increases (+3%, +12%, and +53%) (p < 0.05, all between-treatment comparisons). Fewer patients were administered lipid-lowering therapy in the atazanavir arm (6% vs 20% for lopinavir/ritonavir). Both regimens were safe and well tolerated. CONCLUSIONS: While both treatments demonstrated good antiviral efficacy, relatively greater antiviral suppression was observed with lopinavir/ritonavir. In those patients with no NRTI mutations at baseline, both regimens demonstrated comparable virologic suppression. Atazanavir-treated patients demonstrated a superior lipid profile and required less frequent lipid-lowering treatment.

The effects of prolonged, intracerebroventricular prolactin treatment on luteinizing hormone secretion, catecholaminergic activity and estrous behavior in ewes.

Searching for the role of prolactin (PRL) in controlling gonadotropic axis activity in sheep, we studied the effects of prolonged, intracerebroventricular (i.c.v.) PRL infusion on luteinizing hormone (LH) secretion and catecholaminergic activity in the hypothalamic infundibular nuclei/median eminence (IN/ME) in sexually active ewes during the periovulatory period. Three groups of animals received the following treatments: 1). i.c.v. infusion of PRL at a dose of 200 microg/day (Lower dose, n = 5); 2). i.c.v. infusion of PRL at a dose of 400 microg/day (Higher dose, n = 6), and 3). i.c.v. infusion of the vehicle (control, n = 5). Each dose of PRL was infused in a pulsatile manner, 4 x 50 microg/h and 4 x 100 microg/h, in 30-min intervals, respectively, during four consecutive days before oncoming ovulation. The estrous behavior of ewes following treatments was also monitored as a determinant of the GnRH/LH surge. Two series of blood collections were made in every ewe, the first on the day preceding the infusion (day 0 of the experiment), the second on the day after the infusion (day 5 of the experiment). In addition, on day 5 of the experiment, perfusions of the IN/ME were made by the push-pull method, either in control or lower dose-treated animals. It was shown that a significant (p < 0.01, p < 0.001) increase in tonic LH secretion during the periovulatory period remained in ewes irrespective of the kind of infusion. No statistical differences were found in LH pulse frequency, amplitude, or in the length of the pulse when compared with values from day 0 and 5 of the experiment within each group. A significant (p < 0.001) increase in IN/ME perfusate concentrations of dopamine and noradrenaline metabolites was noted in PRL-treated ewes in comparison with those in the control. The estrous behavior in PRL-treated animals was delayed for a few days, 3.80 +/- 0.80 days at the lower dose (p < 0.01), and 2.83 +/- 0.98 days at the higher dose (p < 0.05) in comparison with the control, 0.20 +/- 0.20 days. These data indicate that maintenance of an increased PRL concentration within the central nervous system (CNS) for a few days before oncoming ovulation has no inhibitory effect on tonic LH secretion. A few-day shift of the preovulatory GnRH/LH surge, as determined by estrous behavior, might, however, be a consequence of the PRL-induced increase in catecholamine turnover in the IN/ME.

The effect of dietary protein restriction on the secretion of LH and FSH in pre-pubertal female lambs.

The effect of restricted dietary protein on the synthesis, storage and release of LH and FSH was studied in pre-pubertal female lambs. The experiment started when the lambs were aged 12 weeks and weighed 26.0+/-1.6 kg. It was conducted for 25 weeks. The lambs were fed isocaloric diets containing either a restricted level of crude protein (8% CP; n=6; treatment R) or an elevated one (18% CP; n=4; treatment E). At 37 weeks of age and before the first oestrous cycle, blood samples were collected over 6 h at 10 min intervals for LH assay. The lambs were slaughtered and their brains recovered and fixed in situ. Immuno-reactive (IR) LH and FSH cells were localised by immunohistochemistry techniques. Messenger RNA analyses used by non-isotope in situ hybridisation with sense and anti-sense riboprobes from beta subunits of LH and FSH cDNA clones. Data were generated using computer analysis to measure the proportion of IR and/or hybridising cells and their optical density for immuno-staining and hybridisation signal. Plasma LH was measured by RIA. The daily live-weight gains were 56.5+/-13.1 g and 97.8+/-14.3 g for R and E lambs, respectively (P<0.05), so that final weights at slaughter were 36.1+/-1.97 kg and 39.1+/-3.44 kg, respectively (P<0.05). The number of cells expressing LH beta mRNA and the optical density of this hybridisation signal was significantly (P<0.001) lower in the R lambs but the number of IR LH positive cells was higher (P<0.001) than for the E lambs. The concentration of LH in the plasma of R sheep was lower (P<0.05) than the E group and this response was associated with a decrease (P<0.05) in LH pulse frequency and amplitude. Dietary protein concentration appeared to have no effect on the IR in FSH cells or on the expression of FSH beta mRNA. In summary, the low protein diet influenced the body weight and weight gain of growing lambs and exerted an inhibitory effect on the synthesis and the release of LH in the pituitary gonadotrophs. No such effect was observed for FSH. It was concluded that the protein concentration of the diet consumed during the growth of female lambs may be an important modulator of processes leading to the pre-pubertal rise in LH.

[Epidemiology of HBV infections and possibilities for therapeutic actions in children and adolescents with end-stage renal failure treated with dialysis]. / Epidemiologia zakazen HBV i mozliwosci dzialan terapeutycznych u dzieci i mlodziezy ze schylkowa niewydolnoscia nerek leczonych nerkozastepczo.

Wide spreading of prophylaxis principles of HBV infections in dialysis centers decreased the HBV infection rate in general population of dialyzed patients in Poland last years. There is neither data concerned with HBV infection epidemiology in children and adolescents, nor data about anti-viral treatment possibilities and effects in this group of dialyzed patients. The aim of the study was evaluating of HBV infection rate in patients of pediatric dialysis centers and analysis of causes of infection and efficacy of treatment. Study was based on data sent in a query-answer by 8 biggest pediatric dialysis centers, all of them treating 210 patients. HBV infection was found much more often (16.6%) than in population of all hemodialyzed patients in Poland. More than 75% non-vaccinated patients was infected before dialysis therapy, remaining were infected during vaccination, before the protecting level of antibodies was gained. Big differences in HBV infection rate among centers are observed. Nowadays HCV infections (more than 40% patients infected) are a bigger issue. Only 10 patients in 5 centers had anti-viral treatment (5 with isolated HBV infection, 5 with mixed HBV/HCV infection). In 9 patients interferon-alpha and in 1 patient lamivudine was administered. Efficacy of interferon-alpha treatment was similar to the population of non-uremic children (33.3% vs. 50% of HBeAg elimination). Majority of patients quite well tolerated the drug. Only in 1 case interferon-alpha treatment had to be ceased because of side effects. In a boy treated with lamivudine, after 3 months elimination of viremia and decrease of ALAT activity was observed. HBV infection in patients of pediatric dialysis centers is still a serious matter. More strict applying of vaccination against hepatitis B before dialysis treatment is needed. The possibility of HBV infections therapy is limited, mostly for economical reasons.

Effect of food manipulation on the neuropeptide Y neuronal system in the diencephalon of ewes.

The expression of neuropeptide Y (NPY), which is involved in the neuromodulatory function associated with animal nutrition, growth and reproduction, depends on the nutritional status. However, the roles of individual components of food are not fully recognised. In this study, we evaluated the effects of dietary protein levels on the diencephalic population of NPY neurones. Female lambs were fed two diets equilibrated energetically but containing 8% protein in restricted diet or 18% protein in elevated diet, for 15 weeks starting with 6 months of age, during the first breeding period. Then, brain tissues were collected, fixed and used for the immunohistochemical localisation of NPY. Detection of NPY in diencephalon sections was followed by the image analysis and expressed as the percent area stained and optical density of immunostaining. Two distinct populations of the immunoreactive NPY perikarya were found, one in the infundibular nucleus; and the other in areas of diencephalon adjacent to the rostral hypothalamus. Long-term feeding the protein restricted diet caused a prominent expression of the immunoreactive material solely in the hypothalamic NPY neurones, particularly in those located in the entire periventricular area and in the infundibular nucleus. Both, percent area exhibiting positive staining and the density of immunoreactive NPY measured in the periventricular subdivision of the paraventricular nucleus were significantly higher (P<0.05) in sheep fed restricted diet, than in sheep fed on elevated diet. This study describes the distribution of NPY neurones in the sheep diencephalon, and shows the relationships between the expression of hypothalamic population of NPY neurones and the level of protein feeding.

Effects of central infusions of neuropeptide Y on the somatotropic axis in sheep fed on two levels of protein.

Effects of infusions of neuropeptide Y (NPY) into 3rd ventricle of growing sheep fed on diets containing restricted (R) or elevated (E) levels of protein on the immunoreactive (ir) somatostatin neurones, ir somatotrophs, growth hormone (GH) concentration in the blood plasma were studied. The long-term restriction of protein in the diet elicited: enhancing irSS content in periventricular perikarya; diminishing irSS stores in the median eminence and elevating the number ir somatotrophs and content of irGH. NPY infusions enhanced the content of irSS in perikarya in sheep fed on E diet and diminished the number of ir somatotrophs and content of irGH of sheep fed on R diet. The R diet as well as NPY infusions caused an increase in GH mean concentrations in the blood plasma. Obtained results suggest that stimulatory effect of restricted feeding and/or NPY action on GH secretion can be due to attenuated SS output. Since dietary restrictions and exogenous NPY have similar influence on the activation of GH secretion, we suggest that NPY could be a neuromodulatory link between nutritional cues and somatotropic axis in sheep.

[Effectiveness of antiviral treatment of patients with chronic hepatitis C (a Polish multicenter study)]. / Efektywnosc leczenia przeciwwirusowego przewleklego zapalenia watroby typu C (wieloosrodkowe badania pòlskie).

Interferon alpha (INF) is routine treatment in patients with chronic hepatitis C. Many controlled investigations were evaluated to establish the optimal schedule of treatment with sustained virological and biochemical response. Recently, multicentre meta-analyses suggest that combination therapy (INF + Ribavirin) was more effective than treatment with interferon alone. The aim of this study was to compare the efficacy of four schedules of antiviral treatment in 445 patients with chronic hepatitis C. Combination therapy (INF + Ribavirin) given for 6 mo. and monotherapy (INF) for 18 mo. were more effective than interferon alone given for 6 mo. Treatment with INF alone for 6 mo. was demonstrated to be insufficient.

[Liver sarcoidosis--a case report]. / Sarkoidoza watroby--opis przypadku.

46-years old woman was diagnosed in Department of Infectious Diseases of Medical Academy in Wroclaw due to dyspeptic disorder, eosinophilia and high AspAT, AlAT, AP and GGTP level in blood serum. Liver biopsy was performed. Hepatic, noncaseating granulomata were found in liver biopsy specimen. Histological changes indicate to liver sarcoidosis.

[Epidemiology and clinical course of HCV infection in children and adolescents with chronic renal failure]. / Epidemiologia i ewolucja kliniczna zakazenia HCV u dzieci i mlodziezy z przewlekla niewydolnoscia nerek.

The aim of the study was to evaluate epidemiology and clinical course of HCV infection in children and adolescents with end-stage renal disease. The study involved 70 patients, aged 1-25 years, 31 M, 39 F: group of 40 dialysed (27 HD, 13 CAPD) and 30 patients suffering from different chronic renal disease as a control group. Anti-HCV antibodies were assayed by EIA 3rd gene (Abbott Diagnostic) and were sought by LIATEK HCV 3rd gene. HCv RNA was detected and measured by a standardised HCV RNA PCR assay (Amplicor Roche). HCV genotypes were identified by InnoLIPA (Innogenetics). HCV infection was diagnosed in 20 (50%) dialysed and in 3 (10%) non-dialysed patients. None of the HCV infected patients presented the clinical symptoms of hepatitis; the mild activity of ALT was observed in 8 cases only. HCV viremia was relatively low: 365 x 103 copies/mL in PD and 110,9 x 103 copies/mL in HD patients. 3 genotypes of HCV were identified: 1a, 1b and 4c/4d. In 3 cases liver biopsy was performed, no cirrhosis was diagnosed.

HBV-DNA level in blood serum as a predictor of good response to therapy with interferon-alpha-2b of patients with chronic hepatitis B.

The prevalence of hepatitis B infection in population in Poland is low and averages 1-1.5%. However, it means that about 380,000 Poles constantly or temporarily replicate HBV. Chronic HBV infection is associated with increased risk of serious liver diseases and it is estimated that 25-40% of patients with chronic hepatitis B will die prematurely of cirrhosis or primary liver cancer. Up to the present, interferon-alpha (IFN-alpha), with low response rate between 25-55% and some limitations of therapy, has been the only available treatment for chronic hepatitis B. A favorable outcome of IFN-alpha therapy is associated with some prognostic factors, not accepted by all investigators, such as low level of HBV-DNA in serum. The aim of this study was to assess the efficacy of therapy with IFN-alpha 2b (Intron A), administered s.c. 5 MU x 3/week for 16 weeks, in 65 patients with chronic hepatitis B, divided into groups according to the baseline HBV-DNA level. Except for serum HBV-DNA level, there were no demographical and biochemical differences between all the treated groups. The patients were followed-up for 12 months. Sustained response (SR) to the therapy (defined as ALAT normalization, loss of detectable HBV-DNA, seroconversion HBeAg to anti-HBeAg and improvement in liver histology) was observed in 16 (57.14%) of patients in the group with HBVDNA level < 1000 pg/ml, in 6 (37.5%) with HBV-DNA level of 1001-3000 pg/ml, in 4 (28.57%) with HBV-DNA level of 3001-5000 pg/ml and only in 2 (28.57%) of patients in group with HBVDNA level > 5000 pg/ml. We conclude that IFN-alpha is particularly useful in therapy of patients with chronic hepatitis B with low levels of HBV-DNA. The baseline HBVDNA level < 1000 pg/ml in serum is the predictor of good response to IFN-alpha therapy.

[Prevalence of anti-HAV antibodies in selected groups of children]. / Czestosc wystepowania przeciwcial anty-HAV w wybranych grupach dzieci.

Hepatitis A is a significant endemic and epidemic disease of global importance. There are few studies on the epidemiology of hepatitis A in Poland. The aim of this study was to investigate the prevalence of the antibodies to HAV (anti-HAV IgG) in children and adolescents living in urban and rural areas. Sera from 377 children were collected: 195 lived in Warsaw and 182 in rural area (voyevodship opolskie). The prevalence of anti-HAV was very low--9.3% and 3.8% respectively. This finding suggest that epidemiological shift from intermediate to low endemicity is possible in Poland and a new policy of prophylaxis hepatitis A may be necessary.

Decrease of enhanced interferon alpha levels in sera of HIV-infected and AIDS patients receiving combined antiretroviral therapy.

In the advanced stages of human immunodeficiency virus (HIV) infection the defective interferon (IFN) responses have been observed. Persisting high lebels of the acid-labile interferons (al-IFNs) have been found in sera of the patients with AIDS. The combined antiretroviral therapy, that included the reverse transcriptase and viral protease inhibitors, resulted in a significant improvement of the clinical state of the majority of HIV-infected patients. In this report we describe the levels of IFNs in 41 HIV patients subjected to the combined treatment. High IFN levels (median 84, up to 576 U/ml) were found in sera of patients classified as the stage C2 or C3 of AIDS before the treatment. The combined therapy resulted in the decrease of IFN levels (median 7.5, up to 24 U/ml) that approached the levels of IFNs detected in the HIV+, A1-A3 stage patients (median 4, up to 36 U/ml). In contrast, the unsuccessful therapy connected with the worsening of the clinical state and the decrease of CD4+ cell count had no effect on the IFNs levels (median 48, up to 96 U/ml). Thus, the measurements of IFN activity in sera may be useful for monitoring the effects of the antiretroviral combined therapy. In sera of the AIDS patients, subjected to the antiviral bioassays, the mixture of the acid-labile and acid-stable form of IFN-alpha, with the prevailing al-IFN-alpha, have been detected.

[Therapeutic efficacy of low-dose alpha interferon therapy in liver cirrhosis associated with HBV]. / Skutecznosc terapeutyczna niskich dawek interferonu alfa w wyrównanej marskosci watroby zwiazanej z zakazeniem HBV.

The aim of this study was the assessment the efficacy and safety of therapy with interferon alpha (Intron A) administered s.c. 3 MU x 3/week for 12 weeks for patients with HBV related liver cirrhosis (Child's class A). Fifteen patients completed therapy and 12 months follow-up. At the end of follow-up sustained response to the therapy, defined by clearance of HBV-DNA, normalization of ALAT activity in serum and improvement in the liver histology was achieved in 46.6% of treated patients. Moreover, among few patients from group of nonresponders (patients without sustained clearance of HBV-DNA) decrease of HBV-DNA level, ALAT activity in serum and improvement in the liver histology were observed. Adverse effects of IFN alpha therapy were typical, but in any case were no necessity terminate the therapy.

Long-term assessment of interferon responses in the HIV+ and AIDS patients.

Impairment of interferon (IFN) system in human immunodeficiency virus (HIV) infection and acquired immunodeficiency syndrome (AIDS) became a basis for searching IFN responses to monitor the disease progression. For detailed investigations 16 HIV+/AIDS patients with at least 4 successively taken blood samples available for IFN determinations were selected. IFN responses were tested in two ways. Firstly, IFN level in plasma was measured. Secondly, capacity of IFN production by leukocytes was evaluated. The latter was determined in the whole blood assay, in which Newcastle disease virus (NDV) and phytohemagglutinin (PHA) were used as IFN-alpha and IFN-gamma inducers, respectively. The levels of IFN induced in whole blood leukocytes varied considerably in all individuals that had been tested. Nevertheless, two patterns of IFN responses were observed. In pattern I, patients had low levels of IFN in plasma and high levels of induced IFN-alpha and IFN-gamma. It was characteristic for 8 patients in good clinical condition. On the contrary, severe disease found in 2 patients was correlated with high levels of IFN in plasma and low levels of induced IFNs (pattern II). In 6 patients IFN responses were classified as intermediate pattern I/II suggesting transition from pattern I to pattern II. A variation of pattern I was found in the case of a patient defined as long-term survivor having relatively low levels of all IFN tested. The results suggested that interferon measurements reflected clinical condition of HIV+ patients showing not only past but also current immune changes.

[Plasma fibronectin in chronic liver disease--marker of fibrosis?]. / Fibronektyna osoczowa w przewleklych chorobach watroby--znacznik wlóknienia?

The determination of fibronectin (FN) concentration in plasma has been performed in the group of 77 patients (60-with various chronic liver diseases, 6-with AIDS IVc, 11-healthy patients). The purpose of this study was: evaluation of the value of plasma FN determination in assessment the degree of liver fibrosis and the degree of liver damage. The obtained results were compared with routine biochemical tests and histopathological picture of liver sections. Among patients with liver diseases, we observed that plasma FN concentration was significantly lower only in the group with decompensated liver cirrhosis, in relation to control group. Non significant lower values of FN was observed in the group of patients with chronic hepatitis, as well as non significant higher ones in the group with cholestasis and fibrosis. It has been concluded that determination of plasma FN concentration has not any importance in evaluation of degree of liver fibrosis and its only one from many functional liver tests.

[Ehrlichiosis: a new infectious disease]. / Erlichioza--nowa choroba zakazna.

Human ehrlichiosis is transmitted by ticks. For the first time it was described in 1987. The ethiologic agent is Ehrlichia chaffeenisis. The course of the disease may be mild, self-limited or sometimes severe finishing with dead. The main symptoms are: fever, leucopenia, thrombocytopenia, or pancytopenia. Tetracyclines are mostly efficient in the treatment.