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I Santos

Publications and source records attributed to I Santos.

At least 19 recordsLinked to original sources
PubMed2005

Liquid chromatography-mass spectrometry using the hydrogen/deuterium exchange reaction as a tool for impurity identification in pharmaceutical process development.

HPLC-MS employing deuterium oxide and common MS-compatible deuterated additives in the mobile phase with electrospray ionization is shown to be a viable approach for the structural elucidation of impurities in pharmaceutically active agents following initial studies with protic mobile phases. This approach incorporates the hydrogen/deuterium (H/D) exchange reaction where deuterium is substituted for hydrogen at labile sites. Some developmental compounds studied include an amide, amine, lipopeptide, indole and methyl sulfone. H/D exchange is rapid and the chromatographic performance using deuterated mobile phases is comparable to protic counterparts.

Caspofungin↗
PubMed2005

A randomized controlled trial investigating the efficacy and safety of switching from a protease inhibitor to nevirapine in patients with undetectable viral load.

OBJECTIVE: To assess the antiviral efficacy and safety of switching from a protease inhibitor (PI) to nevirapine in patients with long-term HIV-1 RNA suppression on PI-containing regimens, and to assess its influence in the adherence to treatment. METHODS: In an open-label multicentre study, 160 HIV-infected patients with undetectable viral load for at least 6 months on a PI-containing regimen were randomized to either continue with their PI regimen (n=79) or replace PI with nevirapine (n=81). Clinical assessment included plasma HIV-1 RNA, blood chemistry, haematology, lymphocyte counts and adverse events reports. Adherence to treatment and lipodystrophy syndrome were assessed by patient self-reporting. RESULTS: Treatment efficacy was equivalent in the two arms, for patients with viral loads either above or below 100 000 HIV-1 RNA copies/mL. The increase in CD4 cell count was significant in both arms (P<0.00001) but the average CD4 cell count at 48 weeks was slightly higher in the nevirapine arm (596 vs. 569; P=0.1588). The number of patients with severe hypertriglyceridaemia (>400 mg/dL) after 48 weeks of treatment decreased in the nevirapine arm (from 11 to six), but increased in the PI arm (from four to 11) and led to treatment discontinuation in two patients. Lipodystrophy changes increased in 15% of patients in the PI arm but decreased in 4% of patients in the nevirapine arm. Finally, although adherence was similar in the two arms, patients reported that it required significantly less effort to stay on treatment in the nevirapine arm. Conclusions The results indicate that switching from PI to nevirapine is as effective as continuing with PI for maintaining viral control, even in patients with baseline viral load above 100,000 copies/mL. In addition, reductions in hypertriglyceridaemia and lipodystrophy and in the effort required to stay on treatment were observed.

Adult↗
PubMed2004

Studies on pharmaceutical ethnobotany in Arrabida Natural Park (Portugal).

An ethnobotanical survey was carried out in Arrabida Natural Park, a Portuguese Protected Area in the Southwest of the Iberian Peninsula, with an area of 10,820 ha. Working with 72 local people, data on medicinal uses of 156 taxa, belonging to 56 botanical families, were obtained and presented, of which 214 uses corresponding to 81 taxa were previously unreported.

Ethnobotany↗
PubMed2004

Synthesis and biological evaluation of silylated mixed-ligand 99mTc complexes with the [PNS/S] donor atom set.

New oxotechnetium complexes of general formula [99mTc(O)(PNS)(S(CH2)nOSiR3)] (4-6) were synthesized by direct reduction of [99mTcO4]- with stannous chloride, in the presence of the tridentate heterofunctionalized phosphine H2PNS and of the monodentate silylated thiols [HS(CH2)nOSiR3] (n = 2, R = Ph (1); n = 3, R = Ph (2); n = 3, R = Et (3)). The mixed-ligand rhenium and technetium complexes of general formula [M(O)(PNS)(S(CH2)nOH)] (n = 2: M = 99mTc, (7), M = Re, (7a); n = 3: M = 99mTc, (8), M = Re, (8a)) were also prepared. All the 99mTc complexes were obtained with high radiochemical purity (> 95%), after purification by HPLC, and were characterized by comparison of their HPLC profiles with the ones obtained for the corresponding Re compounds. The silylated compounds 4-6 are stable in phosphate saline buffer (PBS) pH 7.4, rat plasma, human serum and whole blood, and do not bind to plasmatic proteins, and also do not challenge with glutathione. The biological behavior of [99mTc(O)(PNS)(S(CH2)nOH)] (7, 8) and [99mTc(O)(PNS)(S(CH2)nOSiR3)] (4-6) was studied. The effect of the pH on the cleavage of the O-Si bond in complexes 4-6 was also evaluated.

Animals↗
PubMed2004

Consensus conference on chronic viral hepatitis and HIV infection: updated Spanish recommendations.

Chronic hepatitis B and C represent a leading cause of morbidity and mortality among human immunodeficiency virus (HIV)-infected patients worldwide. New treatment options against both hepatitis B (HBV) and C (HCV) viruses have prompted us to update previous recommendations for the management of coinfected individuals. Fifteen topics (nine related to HCV, five to HBV and one to both viruses) were selected for this purpose. A panel of Spanish experts in the field was invited to review these areas and propose specific recommendations, which were scored according to the Infectious Disease Society of America (IDSA) grading system. These guidelines represent a comprehensive and updated overview on the management of hepatitis B and C in HIV-infected patients.

Anti-HIV Agents↗
PubMed2001

Re tricarbonyl complexes with ligands containing P,N,N and P,N,O donor atom sets: synthesis and structural characterization.

The coordination chemistry of the heterofunctionalized phosphines HPN2 and H2PNO and of an analogue containing a relevant biomolecule, HPN-Pip (Pip = 4-(3-aminopropyl)-1-(2-methoxyphenyl)piperazine), was studied toward the synthon (NE4)2[ReBr3(CO)3]. The complexes isolated, [Re(CO)3(kappa(3)-PN2)], 3, [Re(CO)3Br(kappa(2)-H2PNO)], 4, and [Re(CO)3Br(kappa(2)-HPN-Pip)], 5, are the first examples of Re(I) compounds stabilized by such a combination of donor atoms. All of the compounds are neutral, but the phosphines, depending on the combination of atoms, act as monoanionic and tridentate (3) or as neutral and bidentate (4, 5). The characterization of 3-5 included IR, 1H NMR, and 31P NMR spectroscopy and X-ray crystallographic analysis. Colorless crystals of compounds 3 and 4 were obtained by slow evaporation of a methanolic solution of 3 and from a boiling acetonitrile solution of 4. Compound 3 crystallizes with two molecules of MeOH per asymmetric unit in the monoclinic space group P2(1)/c, a = 10.1237(8) A, b = 9.4959(4) A, c = 28.365(2) A, beta = 98.707(9) degrees, V = 2695.4(3) A(3), Z = 4; 4 crystallizes in the triclinic space group Ponebar, a = 10.0241(9) A, b = 11.2060(10) A, c = 13.0656(12) A, alpha = 84.883(11) degrees, beta = 71.163(10) degrees, gamma = 63.650(9) degrees, V = 1241.19(19) A(3), Z = 2.

Crystallography, X-Ray↗
PubMed2001

[Initial results and 6 month clinical follow-up after implantation of a silicon carbide coated coronary stent].

INTRODUCTION AND OBJECTIVES: To present the initial Spanish experience with the Tenax coronary stent, a laser sculpted from high-precision 316L stainless steel coated with hydrogen rich amorphous silicon carbide that reduces thrombogenecity and improves biocompatibility. PATIENTS AND METHODS: From July 1998 to July 1999, 206 patients (62 +/- 5 years) underwent implantation of 231 Tenax stents in 9 centers as the only revascularization procedure. The most frequent clinical indication was unstable angina (66%), and most of the lesions were complex (class B2 and C). The target vessels were the left anterior descending (51%) and right coronary arteries (36%). The ejection fraction was < 0.5 in 19% cases. RESULTS: Revascularization was complete in 70%, elective in 80%, and the implantation was direct in 25% of the cases. The procedure was successful in all the lesions, reducing stenosis from 62 +/- 16 to 16 +/- 10% and increasing the minimal luminal diameter from 0.81 +/- 0.40 to 2.61 +/- 0.59 mm. The TIMI flow was reduced in 30%, but normalized after the stent in all but one case. The incidence of cardiac events was minimal: 1 acute thrombosis (0.5%) resolved by a new angioplasty and 1 non-Q myocardial infarction (0.5%). At the 6-month clinical follow-up 10% of the patients presented complaints of angina greater than class II, and a new angioplasty was carried out in 1.9% of these cases. CONCLUSION: Clinical and angiographic data suggest that the hydrogenated silicon carbide coating of the Tenax coronary stent may indeed play a beneficial role in patient outcome, and should therefore be evaluated by prospective clinical trials.

Angina, Unstable↗
PubMed2001

Nutrition counseling increases weight gain among Brazilian children.

To assess the impact on child growth of the nutrition-counseling component of the Integrated Management of Childhood Illnesses (IMCI) strategy, a randomized trial was implemented. All 28 government health centers in a Southern Brazil city were paired according to baseline nutritional indicators. One center from each pair was randomly selected and its doctors received 20-h training in nutrition counseling. Thirty-three doctors were included and 12-13 patients < 18 mo of age from each doctor were recruited. The study included testing the knowledge of doctors, observing consultations and visiting the children at home 8, 45 and 180 d after the initial consultation. Maternal knowledge, practices and adherence to nutritional recommendations were assessed, and anthropometric measurements were taken. Day-long dietary intake was evaluated on a subsample of children. Doctors in the intervention group had better knowledge of child nutrition and improved assessment and counseling practices. Maternal recall of recommendations was higher in the intervention than in the control group, as was satisfaction with the consultation. Reported use of recommended foods was also increased. Daily fat intake was higher in the intervention than in the control group; mean daily intakes of energy and zinc also tended to improve. Children 12 mo of age or older had improved weight gain and a positive but nonsignificant improvement in length. Nutrition-counseling training improved doctors' performances, maternal practices and the diets and weight gain of children. The randomized design with blind outcome evaluation strongly supports a causal link. These results should be replicated in other settings.

Brazil↗
PubMed2001

Antifungal activities of two new azasordarins, GW471552 and GW471558, in experimental models of oral and vulvovaginal candidiasis in immunosuppressed rats.

Sordarins constitute a new class of antifungal agents with a novel mechanism of action involving the selective inhibition of fungal protein synthesis. A further evolution of this class of antifungals has led to a new family of sordarin derivatives called azasordarins. The therapeutic efficacies of two new azasordarins, GW471552 and GW471558, were studied in experimental models of oral and vulvovaginal candidiasis in immunosuppressed rats. In all cases rats were immunosuppressed with dexamethasone in the drinking water. Oral candidiasis was established by inoculating 0.1 ml of a yeast suspension containing 5 x 10(8) cells of Candida albicans 4711E with a cotton swab on three alternate days. Vulvovaginal candidiasis was established in ovariectomized and estrus-induced rats by intravaginal inoculation of 10(7) CFU of C. albicans 4711E in 0.1 ml of saline. GW471552 and GW471558 were administered at 1, 5, and 10 mg/kg of body weight via the subcutaneous route. In oral candidiasis, azasordarins were administered each 8 h for 7 consecutive days, while in vaginal candidiasis the compounds were given each 4 h for 3 consecutive days. Antifungal activity of azasordarins was assessed by colony counts and by histological examination 1 day after treatment. In the oral infection model, GW471552 and GW471558 administered at 5 mg/kg significantly reduced (P < 0.05) the number of CFU of C. albicans compared with untreated controls. In addition, GW471552 and GW471558 given at 10 mg/kg eradicated C. albicans from the oral cavities of 100% of infected animals. Against vulvovaginal infection, both compounds showed significant therapeutic efficacy. GW471552 was able to eradicate the vaginal fungal burden at a dose of 10 mg/kg, and it significantly reduced the number of CFU of C. albicans in vaginas of rats treated with a dose of 5 mg/kg (P < 0.05). GW471558 showed greater efficacy, eradicating the fungal burden of 100% of infected rats at a dose of 5 mg/kg and significantly reducing (P < 0.05) the C. albicans vaginal counts even at a dose of 1 mg/kg. In both therapeutic efficacy studies, the histological findings confirmed the microbiological results. The experimental results presented show that the tested azasordarins are effective against oral and vulvovaginal candidiasis in immunosuppressed rats and could be promising antifungal agents for use in humans.

Animals↗
PubMed2001

Antifungal efficacy of GM237354, a sordarin derivative, in experimental oral candidiasis in immunosuppressed rats.

GM237354 is a novel sordarin derivative with a broad spectrum of potent activity against a wide range of fungi. The members of this new class of antifungal agents act as potent inhibitors of fungal protein synthesis. In this study, the therapeutic effects of GM237354 were investigated in a novel experimental oral Candida albicans infection model in immunosuppressed rats. The animals were immunosuppressed with dexamethasone in their drinking water and infected on three alternate days. GM237354 was given three times per day for seven consecutive days at 1.25, 2.5, 5, or 10 mg/kg of body weight per dose. In addition, to provide a preliminary idea of the correlation between regimen administration and therapeutic efficacy, GM237354 was administered to two additional groups of rats at 5 mg/kg once or twice a day for 7 days. The drug efficacy was assessed microbiologically, histologically, and by a morphometric study of lesions. Evident agreement was observed among results obtained by the different methods in all of the animals studied. Microbiologically, the efficacy of GM237354 was determined by measuring the number of C. albicans organisms in the oral cavities of rats in the middle (day 4) and at the end (day 7) of the treatment. GM237354 administered at 5, 7.5, 10, 15, or 30 mg/kg/day for 7 days significantly reduced the number of CFU in the oral cavities of treated rats compared with the number of CFU in the oral cavities of the untreated controls. A significant reduction was also observed when GM237354 was administered at 7.5, 10, 15, or 30 mg/kg/day for 4 days. Furthermore, C. albicans was not detected in oral swabs from any infected rats after 1 week of treatment when GM237354 was administered at 15 or 30 mg/kg/day or after 4 days of treatment at 30 mg/kg/day. Histologically, untreated control animals showed extensive colonization of the epithelium of the dorsal tongue by numerous hyphae. Animals treated with GM237354 at 7.5 mg/kg/day showed small areas with superficial hyphal penetration into the epithelium that produced intraepithelial microabscesses. However, animals treated with GM237354 at 15 mg/kg/day showed multiple regenerative areas of the covering epithelium, and only focalized zones of the tongue surface were occupied by hyphae. No hyphal colonization of the epithelium was seen in rats treated with GM237354 at 30 mg/kg/day and which showed extensive areas of epithelial regeneration of the tongue. The histopathology findings were confirmed by morphometry studies, and the percentage of epithelium occupied by C. albicans hyphae decreased from 17.5% in the control group to 4.8 and 0.1% in animals treated with GM237354 at 7.5 and 15 mg/kg/day, respectively. These results demonstrated that the sordarin derivative GM237354 was effective against experimental oral candidiasis in immunosuppressed rats, and further studies are needed to determine the potential of GM237354 for use in the treatment of this infection in humans.

Animals↗
PubMed2001

[Prevalence and associated factors to rural occupational accidents, Brazil].

OBJECTIVE: To investigate the frequency of rural occupational accidents and its association with potential risk factors. METHODS: The study was carried out in a urban area of Pelotas, RS, Brazil. A cross-sectional study was conducted. A representative sample of rural workers was selected using a multi-stage sampling. From January to April 1996, a total of 258 rural families were visited and all the 580 rural workers identified in those households answered a standardized questionnaire. RESULTS AND CONCLUSIONS: The prevalence of rural occupational accidents was 11%. After allowing for potential confounders, the main occupational hazards, as shown by logistic regression, were lower socioeconomic status (OR=1.81), non-white skin color (OR=3.50), and poor work satisfaction (OR=2.77).

Accidents, Occupational↗
PubMed2001

Long-term (four years) follow-up of patients with treated nocturnal hypertension assessed by ambulatory blood pressure monitoring.

STUDY OBJECTIVE: Nocturnal Hypertension (NH) is an independent risk factor for cardiovascular morbidity and mortality (M-M). However, an inappropriate decrease in diastolic BP during the night significantly increases morbidity. There are no prospective studies on the long-term consequences on M-M in treated NH. We accordingly studied M-M in 107 consecutive patients with treated NH, assessed by ambulatory blood pressure monitoring (ABPM), during a four-year follow-up. PATIENTS AND METHODS: From the initial 107 patients six died (5 from brain or cardiovascular causes). In 65 patients it was possible to repeat the ABPM during the follow-up period. They were hypertensive patients class I-II (JNC IV) 62 +/- 10 years old, 56 were male and were observed before and after starting treatment on a four-year follow-up period. We considered age, sex, body mass index, previous cerebral and cardiovascular accidents, type and number of drugs administered, smoking habits, plasma cholesterol, glycemia, and causal and ambulatory blood pressure monitoring (ABPM) (24 hr, 6 am-10 am, 10 pm-6 am and pulse pressure) before and after follow-up, dipper status and the period of follow-up. RESULTS: The patients whom died were older and had a significantly higher systolic blood pressure compared to the survivors. We considered two groups: with (A - n = 18) or without (B - n = 47) cerebral and cardiac morbidity. The A group had more previous cerebral and cardiovascular accidents (p = 0.05), a more intensive treatment (p = 0.02), and a greater fall in diastolic blood pressure (DBP) during the night in both absolute and percentage numbers, after treatment, than the B group. However, after regression analysis, the only independent risk marker differentiating between the two groups was the percentage fall in the DBP after treatment (dipper phenomenon) (p = 0.01). CONCLUSIONS: In 65 treated hypertensive (NH) patients assessed by ABPM before and after treatment (four-year follow-up) we identified a group with cerebral and cardiovascular morbidity. These patients, in contrast with another group with no morbidity, had more previous cerebral and cardiovascular accidents, they were more intensively treated, and they had a greater fall in diastolic blood pressure after therapy (absolute and percentage values). However, after regression analysis the diastolic nocturnal blood pressure dipper phenomenon after treatment was the only risk marker associated with morbidity. In such cases it is possible that treatment guided by ABPM can decrease morbidity.

Aged↗
PubMed2001

[Is ambulatory blood pressure monitoring reliable in hypertensive patients with atrial fibrillation?].

Atrial fibrillation (AF) is commonly seen in patients (pts) with systemic hypertension. They are usually excluded from ambulatory blood pressure monitoring (ABPM) because its accuracy is unknown. The aim of our study was to determine if ABPM can be used to assess 24 hour BP in pts with AF. We included hypertensive pts with chronic (> 6 months) AF, controlled heart rate (60-100 c.p.m), under therapy and also hypertensive pts in sinus rhythm (control group--CG). They were submitted to 24 hour ABPM (Spacelabs 90207). Manual BP with a standard mercury sphygmomanometer was taken during 3 visits (office BP) and on the day of ambulatory monitoring. Simultaneous measurements with a T-Tube were also performed. Thirty pts with chronic AF (63% males), mean age 73 +/- 8 years (52-85) and 18 pts in sinus rhythm (CG) were studied. The age, gender, office BP, ambulatory BP and proportion of successful measurements was similar in the 2 groups. In CG systolic and diastolic office BP did not differ from day ambulatory BP (148 +/- 14/84 +/- 7 vs 138 +/- 18/76 +/- 11 mmHg) and the same was seen in pts in AF (table). In this group, only the systolic BP taken immediately before the ambulatory device was put on, was significantly different from day ambulatory BP (148 +/- 21 vs 137 +/- 19 mmHg, p = 0.04). The proportion of successful measurements in AF group was 94 +/- 8 (65-98) with 93% > 80%. In 64 simultaneous measurements the differences were 6 +/- 5 and 5 +/- 5 mmHg for systolic and diastolic BP. Casual and ambulatory heart rate was also similar in the two groups (76 +/- 7/76 +/- 12--AF group; 78 +/- 10/78 +/- 8--control group). In conclusion, this study demonstrates that ABPM can be used to assess BP in patients with atrial fibrillation. There was a high percentage of successful recordings (93%). As in patients in sinus rhythm, there was no significantly difference in mean office blood pressure and daytime ambulatory blood pressure.

Aged↗
PubMed2000

Cationic Re(V) oxo complexes with poly(pyrazolyl)borates: synthesis, characterization, and stability.

Cationic Re(V) oxo compounds of the type [ReO(OSiMe3)(eta 2-B(pz)4)(L)2]X [X = Cl, L = 4-(NMe2)C5H4N (1), 1-Meimz (1-methylimidazole; 2), 1/2 dmpe (1,2-bis(dimethylphosphino)ethane; 3), py (4a); X = I, L = py (4b)] can be prepared by reacting trans-[ReO2(eta 2-B(pz)4)(L)2] with XSiMe3. In solution, cations 1-4 are reactive species, and those with unidentate nitrogen donor ligands (1, 2, and 4) rearrange into the neutral derivatives [ReO(Cl)(OSiMe3)(eta 2-B(pz)4)(L)] [L = py (5), 4-(NMe2)C5H4N (6), 1-Meimz (7)], which are also reported herein. Compounds 1-3 and 5-7 have been fully characterized by the usual spectroscopic techniques, which in some cases includes X-ray crystallographic analysis (3, 6, and 7). Compound 3 crystallizes from CH2Cl2/n-hexane as yellow crystals with one molecule of CH2Cl2 solvent, and compounds 6 and 7 crystallize from THF/n-hexane as violet and red crystals, respectively, with one molecule of THF solvent in the case of 6. Crystallographic data: 3, orthorhombic space group Pn2(1)a, a = 11.311(2) A, b = 19.135(2) A, c = 15.443(2) A, V = 3342.4(8) A3, Z = 4; 6, triclinic space group P1, a = 8.7179(11) A, b = 12.5724(8) A, c = 17.750(2) A, alpha = 70.454(7) degrees, beta = 77.935(9) degrees, gamma = 77.129(8) degrees, V = 1768.1(3) A3, Z = 2; 7, monoclinic space group P2(1)/c, a = 16.356(2) A, b = 20.384(3) A, c = 17.360(3) A, beta = 106.971(12) degrees, V = 5535.8(14) A3, Z = 8.

Journal Article↗
PubMed2000

Cryofibrinogenaemia with a good response to stanozolol.

We report a 63-year-old patient with an IgA-kappa multiple myeloma in complete remission who developed necrotic lesions on both ears and papular, purpuric lesions on his legs and cheeks. Initial differential diagnosis included perniosis and skin necrosis secondary to interferon treatment but subsequent investigation revealed cryofibrinogenaemia as the underlying cause. Stanozolol therapy, 2 mg/12 h, achieved a complete clearance of the skin lesions. Cryofibrinogenaemia is a disease which can be under-diagnosed unless it is considered in the work-up of a patient with thrombotic skin lesions. Stanozolol is useful as first line therapy for this disorder.

Anabolic Agents↗
PubMed2000

Transgenic mice expressing bovine GH develop arthritic disorder and self-antibodies.

We observed disability of movement in 6-month-old transgenic mice expressing the fusion gene coding for the bovine GH (bGH) under the transcriptional control of phosphoenolpyruvate carboxykinase promoter (PEPCK-bGH). Histological study of the knee joint showed altered synovial and tibial articular cartilage tissues. In the cartilage the following observations were made: (i) generalized loss of the normal zonal structure and presence of clefts, and (ii) profound alterations in chondrocyte growth/differentiation processes consistent with hypertrophy. The synovial tissue showed a reduced number of adipocytes, and a significant thickening of synovial lining tissue and pannus. These findings indicate that transgenic mice suffer damage to diarthritic joints with osteoarthritic appearance. As changes in synovial membrane in osteoarthritis are almost indistinguishable from those seen in inflammatory arthritis, we determined the potential correlation with an immunological disorder. Serological determination of self-antibodies measured as a function of age and sex showed anti-nuclear, anti-single-stranded DNA, anti-double-stranded DNA and anti-70K antibodies, and an altered immunoglobulin typing. These results suggest that transgenic mice expressing bGH develop an arthritic process which is correlated with an immune disorder. The results also indicate that these mice are a suitable animal model to study the specific role of GH-driven processes in immune cells and arthritis.

Animals↗
PubMed1999

Immunochemotherapy with interferon-gamma and multidrug therapy for multibacillary leprosy.

Treatment for multibacillary leprosy is presently performed with a multidrug therapy (MDT) scheme maintained for 2 years. Leprosy treatment however can benefit from the reduction of length. The lack of interferon-gamma (IFN-gamma) production by lepromatous leprosy (LL) patients' lymphocytes lead us to use this cytokine in the treatment of multibacillary leprosy associated with MDT in the treatment of multibacillary leprosy, and monitor several clinical and immunological parameters during the course of treatment. A total of 20 multibacillary leprosy patients were evaluated, 10 treated with MDT alone, and 10 treated with MDT + 10 daily doses of 2 x 10(6) international units (IU) of recombinant human IFN-gamma/m2 followed by 10 daily doses of 10(7) IU IFN-gamma/m2, intramuscularly, during the first 20 days of MDT. IFN-gamma was well tolerated and did not cause any increase in the rate of leprosy reactions development during treatment. Decrease of bacillary load, fall of anti-Mycobacterium leprae IgG serum antibodies, changes of histological pattern, as well as changes in lymphocyte proliferation assay in response to mitogens (PHA or PWM), M. leprae antigen or PPD was similar in both groups of patients. Among several soluble immunological markers measured before and 30 days after beginning of treatment, levels of soluble IL-2R receptor increased in patients treated with MDT plus IFN-gamma whereas decreased in patients treated with MDT alone. Soluble ICAM-1 levels decreased in the MDT group but did not change in the MDT + IFN-gamma treated patients. Soluble CD4 and soluble CD8 markers did not change significantly in either group of patients. Neopterin, a marker of macrophage activation, increased in all but one patient treated with MDT + IFN-gamma but in none treated with MDT alone, indicating that IFN-gamma was active in vivo. Our findings indicate that despite being able to promote macrophage activation in multibacillary leprosy patients a short course of systemically administered IFN-gamma is not able to change the clinical course of a long standing disease such as leprosy.

Adolescent↗