Production of septal fibrosis of the liver by means of foreign protein injections into rats

Similarities and differences in antigenic humoral responses and electrophoretic patterns between Capillaria hepatica and pig-serum were investigated as a contribution to the understanding of hepatic fibrosis induced by the parenteral administration of foreign proteins. Only two out of 10 rats receiving repeated intraperitoneal injections of an extract of Capillaria hepatica-infected mouse liver presented septal hepatic fibrosis (20%). Under the same experimental conditions, 4 out of 9 rats (44.4%) developed septal fibrosis following whole pig-serum administration. Injections of normal mouse liver extracts did not result in hepatic fibrosis. Since a 100% septal fibrosis rate is observed in experimentally Capillaria hepatica-infected rats, it appeared that Capillaria hepatica products continuously released from inside the liver creates a much more effective fibrosis inducing mechanism than the parenteral administration of such factors. Thus, repeated peritoneal administration of a foreign protein to rats would not reveal the full fibrogenic potential it may have under natural conditions.

Assesment of the treatment of earlobe keloids with triamcinolone injections, surgical resection, and local pressure

OBJECTIVE: To evaluate the combined treatment of ear lobe keloids. METHODS: We studied 46 consecutive patients with 81 ear lobe keloids. Patients underwent local infiltration of triamcinolone acetonide (TCN) at concentrations of 40mg/ml (Group 1), 20 mg/ml (Group 2) and 10mg/ml (Group 3). The volume of TCN infiltrate varied according to the size of the lesion. Treatment consisted of three monthly injections before surgery, excision of keloid in the fourth month and perioperative infiltration, followed by two more leaks TCN within two months. Patients used earrings pressure on the scar after operation for four months. The pressure exerted by earrings in the ear lobe was measured electronically. Post-treatment follow-up of patients was 24 months. RESULTS: TCN at concentrations of 20mg/ml and 40mg/ml were effective for the treatment of keloids, no difference between the groups (p = 0.58). However, patients in which TCN was infiltrated the 10mg/ml had poor involution of keloid and the study of this group was stopped. CONCLUSION: the combination of infiltration TCN month to 20 mg/mL (1.2mg to 2.0mg per mm3 TCN injury), surgical excision and pressure application device is effective for treatment of keloid ear lobe.

Opiatergic participation in the thirst-inhibiting effect of acute third ventricle injections of cadmium (Cd2+) and lead (Pb2+)

We have previously demonstrated that acute third ventricle injections of both lead and cadmium prevent the dipsogenic response elicited by dehydration or by central injections of dipsogenic agents such as angiotensin II, carbachol and isoproterenol in rats. We have also shown that the antidipsogenic action of cadmium may be due, at least in part, to activation of thirst-inhibitory central serotonergic pathways. In the present paper we show that in Wistar male rats the antidipsogenic effect of both lead acetate (3.0 nmol/rat) and cadmium chloride (3.0 nmol/rat) may be partially dependent on the activation of brain opiatergic pathways since central injections of naloxone (82.5 nmol/rat), a non-selective opioid antagonist, blunt the thirst-inhibiting effect of these metals. One hundred and twenty minutes after the second third ventricle injections, dehydrated animals (14 h overnight) receiving saline + sodium acetate displayed a high water intake (7.90 ± 0.47 ml/100 g body weight) whereas animals receiving saline + lead acetate drank 3.24 ± 0.47 ml/100 g body weight. Animals receiving naloxone + lead acetate drank 6.94 ± 0.60 ml/100 g body weight. Animals receiving saline + saline drank 8.16 ± 0.66 ml/100 g body weight whilst animals receiving saline + cadmium chloride drank 1.63 ± 0.37 ml/100 g body weight. Animals receiving naloxone + cadmium chloride drank 8.01 ± 0.94 ml/100 g body weight. It is suggested that acute third ventricle injections of both lead and cadmium exert their antidipsogenic effect by activating thirst-inhibiting opioid pathways in the brain.

Effects of intracutaneous injections of sterile water in patients with acute low back pain: a randomized, controlled, clinical trial

Intracutaneous sterile water injection (ISWI) is used for relief of low back pain during labor, acute attacks of urolithiasis, chronic neck and shoulder pain following whiplash injuries, and chronic myofascial pain syndrome. We conducted a randomized, double-blinded, placebo-controlled trial to evaluate the effect of ISWI for relief of acute low back pain (aLBP). A total of 68 patients (41 females and 27 males) between 18 and 55 years old experiencing aLBP with moderate to severe pain (scores ≥5 on an 11-point visual analogue scale [VAS]) were recruited and randomly assigned to receive either ISWIs (n=34) or intracutaneous isotonic saline injections (placebo treatment; n=34). The primary outcome was improvement in pain intensity using the VAS at 10, 45, and 90 min and 1 day after treatment. The secondary outcome was functional improvement, which was assessed using the Patient-Specific Functional Scale (PSFS) 1 day after treatment. The mean VAS score was significantly lower in the ISWI group than in the control group at 10, 45, and 90 min, and 1 day after injection (P<0.05, t-test). The mean increment in PSFS score of the ISWI group was 2.9±2.2 1 day after treatment, while that in the control group was 0.9±2.2. Our study showed that ISWI was effective for relieving pain and improving function in aLBP patients at short-term follow-up. ISWI might be an alternative treatment for aLBP patients, especially in areas where medications are not available, as well as in specific patients (e.g., those who are pregnant or have asthma), who are unable to receive medications or other forms of analgesia because of side effects.

Polio inactivated vaccine costs into routine childhood immunization in Brazil

OBJECTIVE To analyze the costs of vaccination regimens for introducing inactivated polio vaccine in routine immunization in Brazil.METHODS A cost analysis was conducted for vaccines in five vaccination regimens, including inactivated polio vaccine, compared with the oral polio vaccine-only regimen. The costs of the vaccines were estimated for routine use and for the “National Immunization Days”, during when the oral polio vaccine is administered to children aged less than five years, independent of their vaccine status, and the strategic stock of inactivated polio vaccine. The presented estimated costs are of 2011.RESULTS The annual costs of the oral vaccine-only program (routine and two National Immunization Days) were estimated at US$19,873,170. The incremental costs of inclusion of the inactivated vaccine depended on the number of vaccine doses, presentation of the vaccine (bottles with single dose or ten doses), and number of “National Immunization Days” carried out. The cost of the regimen adopted with two doses of inactivated vaccine followed by three doses of oral vaccine and one “National Immunization Day” was estimated at US$29,653,539. The concomitant replacement of the DTPw/Hib and HepB vaccines with the pentavalent vaccine enabled the introduction of the inactivated polio without increasing the number of injections or number of visits needed to complete the vaccination.CONCLUSIONS The introduction of the inactivated vaccine increased the annual costs of the polio vaccines by 49.2% compared with the oral vaccine-only regimen. This increase represented 1.13% of the expenditure of the National Immunization Program on the purchase of vaccines in 2011.

Active immunization against hepatitis B virus (HBV) with low-doses of plasma-derived vaccine by intradermal route

Schedule for vaccination against HBV infection has usually been based on three separate injections of 20 meg of the vaccine by intramuscular route. One of the main shortcomings to its use in large scale programs has been its high cost. Ninety out of 300 health workers were submitted to three injections of 2 meg of plasma-derived vaccine (PDV) by intradermal (ID) route on days 0, 30, and 180. Anti-HBs was detected in 74 (82.2%) after the second dose and in 80 (88.9%) after the third dose, a non-significant difference. However, levels above 10 times the cut-off were observed in 29 (32.2%) and 77 (85.5%), respectively (p < 0.001). The results showed that a low-dose schedule is effective when used in health workers and should be tried with other risk groups.

Histological observations on Montenegro's reaction in man

The Montenegro skin test is widely used as a diagnostic method for American cutaneous leishmaniasis (ACL) but little is known about the histological changes that occur in the skin after administration of the antigen. This report is based on histological studies of biopsied material obtained, from inoculation sites, 48 hours after individuals had been given intradermal injections with a standardized Montenegro antigen. The material examined was obtained from four distinctly different test groups: naturally infected patients with parasitologically proved ACL and with positive Montenegro's reaction; individuals without previous history of ACL and not previously tested with Montenegro antigen; participants in anti-ACL vaccine trials who developed positive reactions to Montenegro antigen after vaccination; other participants in vaccine trials who had negative Montenegro responses after vaccination or had served as controls in the trials. The histological pictures of each group are described and discussed. Histologically, the reactions of vaccinated individuals were indistinguishable from those with naturally acquired infections.

Modulation of parasitemia and antibody responce to Trypanosoma cruzy by cyclophosphamide in Calomys callosus (Rodentia, Cricetidae)

Calomys callosus a wild rodent, previously described as harboring Trypanosoma cruzi, has a low susceptibility to infection by this protozoan. Experiments were designed to evaluate the contribution of the immune response to the resistance to T. cruzi infection exhibited by C. calossus. Animals were submitted to injections of high (200 mg/kg body weight) and low (20 mg/kg body weight) doses of cyclophosphamide on days -1 or -1 and +5, and inoculated with 4 x 10³ T. cruzi on day O. Parasitemia, mortality and antibody response as measured by direct agglutination of trypomastigotes were observed. Two hundred mg doses of cyclophosphamide resulted in higher parasitemia and mortality as well as in suppression of the antibody response. A single dose of 20 mg enhanced antibody levels on the 20th day after infection, while an additional dose did not further increase antibody production. Parasitemia levels were not depressed, but rather increased in both these groups as compared to untreated controls. Passive transfer of hyperimmune C. callosus anti-T. cruzi serum to cyclophosphamide immunosuppressed animals resulted in lower parasitemia and mortality rates. These results indicate that the immune response plays an important role in the resistance of C. callossus to T. cruzi.

Reduced schedule of human anti-rabies immunization with Fuenzalida & Palacios vaccine: additional data

It was reevaluated a reduced schedule for anti-rabies post-exposure immunization with newborn mice nervous tissue vaccine (Fuenzalida 8c Palacios) in a group of 30 non exposed volunteers. The vaccine was administered by intramuscular injections on days zero, 2, 4, 16 and 27, in the deltoid area. Antibody levels were determinated by a simplified serum neutralization microtest on days zero, 16 and 37. On days 16 and 37 the antibody levels of the whole group was >0.5 IU/ml and >1.0 IU/ml, respectively. The cell mediated immunity was precociously detected (on day 4) by the delayed type hipersensitivity skin test. Our results show that this reduced schedule elicited an early and effective humoral and cellular immune response. However it is necessary other studies with larger groups of vaccinees in order to obtain definitive conclusion.

Intranasal sensitization with Blomia Tropicalis antigens induces allergic responses in mice characterized by elevated antigen-specific and non-specific serum ige and peripheral blood eosinophil counts

In order to evaluate the potential allergenicity of Blomia tropicalis (Bt) antigen, IgE production of both specific and non-specific for Bt antigen was monitored in BALB/c mice after exposure to the antigen by nasal route. It was evidenced that B. tropicalis contains a functional allergen in its components. The allergenic components, however, when administered intranasally without any adjuvant, did not function to induce IgE response within a short period. On the other hand, intranasal inoculation of Bt antigens augmented serum IgE responses in mice pretreated by a subcutaneous priming injection of the same antigens. Inoculation of Bt antigen without subcutaneous priming injections induced IgE antibody production only when the antigen was continuously administered for a long period of over 24 weeks. Even when the priming injection was absent, the Bt antigen inoculated with cholera toxin (CT) as a mucosal adjuvant also significantly augmented the Bt antigen-specific IgE responses depending on the dose of CT co-administered. The present study also demonstrated that Bt antigen/CT-inoculated mice showed increased non-specific serum IgE level and peripheral blood eosinophil rates without noticeable elevations of the total leukocyte counts. The immunoblot analysis demonstrated 5 main antigenic components reactive to IgE antibodies induced. These components at about 44-64 kDa position were considered to be an important candidate antigen for diagnosis of the mite-related allergy.

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

An intermittent schedule is better than continuous regimen of antimonial therapy for cutaneous leishmaniasis in the municipality of Rio de Janeiro, Brazil

This study reviews a series of cutaneous leishmaniasis cases diagnosed and treated in outpatient units in the municipality of Rio de Janeiro, where the intermittent schedule of antimonial therapy was replaced by the continuous regimen. Both schedules were based on daily intramuscular injections of pentavalent antimonial. Forty-nine subjects received the intermittent regimen, consisting of three ten-day series alternated with ten-day rest intervals whereas seventy-one patients received the continuous regimen during 20 consecutive days. The study groups had similar composition regarding age, sex and clinical condition. The cure rate was significantly higher in the group receiving the intermittent schedule than in the group receiving continuous therapy (89.8% vs 63.3%). Moreover, loss to follow-up was significantly more frequent in the group receiving continuous therapy (19.7% vs 4.1% in the intermittent therapy). Under field conditions, the intermittent regimen provided higher effectiveness and adherence than the continuous schedule.

An alternative antimonial schedule to be used in cutaneous leishmaniasis when high doses of antimony are undesirable

Despite more than half a century of use in leishmaniasis, antimony therapy still presents serious problems concerning dosage and toxicity. Low and high doses have been shown to be equally effective. In this paper, the feasibility of injecting one ampoule of meglumine antimoniate intramuscularly every other day until clinical cure is demonstrated, while studying a series of 40 cutaneous leishmaniasis cases. Total dose used varied from 1,822.5 to 12,150mg of pentavalent antimony and total time of treatment varied from 3 to 10 weeks, with 86% efficacy. Thirty-six out of the 40 patients are still on follow-up with a mean time of 10.7 ± 7 months and a median of 9 months. No relapse or mucosal lesions have been noted so far. The schedule showed good tolerance and easy application and its efficacy was comparable to the officially recommended WHO schedule. Therefore, such a schedule represents a valuable alternative for the cases with high toxicicity to antimony or daily injections are an obstacle to the treatment.

The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis in the golden hamster model

New therapeutic alternatives against leishmaniasis remain a priority. The activity of azithromycin against Leishmania (Leishmania) major has been previously demonstrated. Different responses among species of Leishmania make species-specific drug screening necessary. The activity of azithromycin against Leishmania (Viannia) braziliensis and Leishmania (Leishmania) amazonensis was evaluated in golden hamsters infected through footpad injections of metacyclic promastigotes, and compared with untreated controls and animals treated with meglumine antimoniate. Footpad thickness, lesion cultures and dissemination sites were analyzed. Treatment of golden hamsters with oral azithromycin at 450mg/kg had no activity against infections with Leishmania (Leishmania) amazonensis. For infections due to Leishmania (Viannia) braziliensis, azithromycin demonstrated significant activity relative to untreated controls, but inferior to meglumine antimoniate, for controlling lesion size. Neither drug was able to totally eliminate parasites from the lesions. It was concluded that azithromycin has activity against Leishmania (Viannia) braziliensis but not against Leishmania (Leishmania) amazonensis in this model.

A regulação do lobo anterior da hypophyse por um hormonio testicular, especialmente sob o ponto de vista morphologico

The authors summarize the results of former works, based on the technics of parabiosis. After parabiotic union of two infantile rats, normal + castrate, the normal fellow enters into precocious puberty in about 7 days (Kallas). In the case of pairs: castrated male + normal female, the implants of testicles, or injection of maceration or aqueous extracts of testis in the castrated fellow, prevents the induction of early puberty in the normal female. In the case: castrated female + normal female, no inhibiting effect is provoked by that treatment. There is therefore a testicular hormone that regulates the hypophysis. After castration, this gland manifests a hyper-function and shows histological alterations, the chief character of these being the appearing in the anterior lobe, of the so-called castration cells, probably originated from basophile cells. Implants or injections of testis material prevent those alterations. This is a useful test; the effect is controlled by estimating the castration cells in the microscopic field. The testicular hormone that regulates the anterior lobe is probably another one, quite different from that which regulates the accessory genitalia. On account of the facts and experiments, it may be assumed that this new hormone is elaborated by the germinal epithelium of the testicles.