Topical 15% Paromomycin-Aquaphilic for Bolivian Leishmania braziliensis Cutaneous Leishmaniasis: A Randomized, Placebo-controlled Trial.

BACKGROUND: Cutaneous leishmaniasis (CL) presents as 1 or more skin lesions, which makes local therapy inherently attractive compared to systemic therapy that exposes the whole body to a drug. For 30 years, 15% paromomycin topical formulations have been in clinical experimentation. Recently, 15% paromomycin in Aquaphilic, a complex base to facilitate adsorption into the lesion, was found superior to aquaphilic vehicle for Old World Leishmania major disease. METHODS: We performed a randomized trial of 15% paromomycin in Aquaphilic (40 patients) vs Aquaphilic vehicle (20 patients) vs a positive control (intralesional pentamidine; 20 patients) against L. braziliensis CL in Bolivia. RESULTS: Cure rates after 6 months of follow-up were 31 of 40 (77.5%, 95% confidence interval [CI] 62.5-88%) for paromomycin-Aquaphilic, 2 of 20 (10%, 95% CI 3-30%) for Aquaphilic vehicle (P < .0001 vs paromomycin-Aquaphilic), and 14 of 20 (70%, 95% CI 48-85.5%) for intralesional pentamidine. Both paromomycin-Aquaphilic and the Aquaphilic vehicle were very well tolerated, with only grade 1 adverse reactions in 5-10% of patients. CONCLUSIONS: Against L. braziliensis CL, a prevalent, aggressive form of New World CL, 15% paromomycin-aquaphilic was vastly superior to a negative vehicle control and was comparable in efficacy to a positive control. This study enlarges the potential use of 15% paromomycin-Aquaphilic from one form of Old World CL to CL more generally. CLINICAL TRIALS REGISTRATION: NCT03096457.

Oral Health-Related Quality of Life in an Institutionalized Population with HIV+/AIDS in the Northern Region of Mexico.

Approximately 39 million people worldwide live with human immunodeficiency virus (HIV), and antiretroviral therapy (ART) has improved life expectancy for these individuals, with quality of life (QoL) being a crucial aspect. However, there is limited information on oral health-related quality of life (OHRQoL) for institutionalized patients with HIV. This study used a cross-sectional design and included 43 residents of a non-governmental institution who had a confirmed HIV diagnosis and a history of intravenous drug use. The Spanish version of the Oral Health Index Profile-14 (OHIPsp) was used to assess the OHRQoL, with the 50th percentile serving as the cutoff for good or poor quality of life. All 43 patients had one or more oral lesions, with 44.1% having AIDS-related oral lesions (AROLs). Over half of the participants (48.8%) reported a poor OHRQoL, and females experienced worse quality of life in all dimensions compared to males. Subjects with AROLs were three times more likely to have poor OHRQoL than those without AROLs (p = 0.03; OR = 3.1 IC 1.04-9.6). These results highlight the need for a comprehensive treatment plan for patients with HIV that includes oral health, particularly for women living in precarious conditions or who are institutionalized. Improving oral health can significantly enhance quality of life.

Intralesional antimony for single lesions of bolivian cutaneous leishmaniasis.

BACKGROUND: Cutaneous leishmaniasis is an ultimately self-curing disease for which systemic therapy with pentavalent antimony (Sb) is effective but with side effects. We evaluated 2 local treatments, intralesional (IL) Sb and cryotherapy, for single lesions due to Bolivian Leishmania (v.) braziliensis in a placebo-controlled study. METHODS: Patients were randomized between IL Sb (650 µg/mm(2) of lesion area on days 1, 3, and 5), cryotherapy (days 1 and 14), and placebo cream (daily for 20 days) in a 3:2:3 allocation. Lesion area was measured prior to therapy, and at 1, 3, and 6 months after therapy. The criteria for lesion cure were as follows: not doubling in size at 1 month, at least 50% diminution in size at 3 months, and complete reepithelialization at 6 months. Local adverse effects were recorded. RESULTS: Cure rates were 21 of 30 (70%; 95% confidence interval [CI], 52%-83%) for IL Sb, 4 of 20 (20%; 95% CI, 8%-42%) for cryotherapy, and 5 of 30 (17%; 95% CI, 7%-34%) for placebo cream (P < .001 for IL Sb vs each other group). IL Sb adverse events were limited to injection site pain, with a mean value of 1.0 (mild). CONCLUSIONS: The comparative cure rate, small amount of drug administered, and tolerance data for IL Sb suggest that if local therapy for single L. braziliensis lesions is chosen, this treatment is attractive. Given the difficulties of performing placebo-controlled trials in the New World, the combined placebo and cryotherapy cure rate (18%; 95% CI, 10%-31%) is likely to become the standard against which future interventions for L. braziliensis are compared. CLINICAL TRIALS REGISTRATION: NCT01300975.

Cutaneous leishmaniasis treatment and therapeutic outcomes in special populations: A collaborative retrospective study.

BACKGROUND: Treatment guidance for children and older adult patients affected by cutaneous leishmaniasis (CL) is unclear due to limited representation of these groups in clinical trials. METHODS: We conducted a collaborative retrospective study to describe the effectiveness and safety of antileishmanial treatments in children ≤ 10 and adults ≥ 60 years of age, treated between 2014 and 2018 in ten CL referral centers in Latin America. RESULTS: 2,037 clinical records were assessed for eligibility. Of them, the main reason for non-inclusion was lack of data on treatment follow-up and therapeutic response (182/242, 75% of children and 179/468, 38% of adults). Data on 1,325 eligible CL patients (736 children and 589 older adults) were analyzed. In both age groups, disease presentation was mild, with a median number of lesions of one (IQR: 1-2) and median lesion diameter of less than 3 cm. Less than 50% of the patients had data for two or more follow-up visits post-treatment (being only 28% in pediatric patients). Systemic antimonials were the most common monotherapy regimen in both age groups (590/736, 80.2% of children and 308/589, 52.3% of older adults) with overall cure rates of 54.6% (95% CI: 50.5-58.6%) and 68.2% (95% CI: 62.6-73.4%), respectively. Other treatments used include miltefosine, amphotericin B, intralesional antimonials, and pentamidine. Adverse reactions related to the main treatment were experienced in 11.9% (86/722) of children versus 38.4% (206/537) of older adults. Most adverse reactions were of mild intensity. CONCLUSION: Our findings support the need for greater availability and use of alternatives to systemic antimonials, particularly local therapies, and development of strategies to improve patient follow-up across the region, with special attention to pediatric populations.

Investigation on the protective effects of cranberry against the DNA damage induced by benzo[a]pyrene.

There are few reports that demonstrate the antigenotoxic potential of cranberries. Although the types of berry fruits consumed worldwide are many, this paper focuses on cranberries that are commonly consumed in Mexico (Vaccinium macrocarpon species). The purpose of the present study is to determine whether cranberry ethanolic extract (CEE) can prevent the DNA damage produced by benzo[a]pyrene (B[a]P) using an in vivo mouse peripheral blood micronucleus assay. The experimental groups were organized as follows: a negative control group (without treatment), a positive group treated with B[a]P (200 mg/kg), a group administered with 800 mg/kg of CEE, and three groups treated with B[a]P and CEE (200, 400, and 800 mg/kg) respectively. The CEE and benzo[a]pyrene were administered orally for a week, on a daily basis. During this period the body weight, the feed intake, and the determination of antigenotoxic potential were quantified. At the end of this period, we continued with the same determinations for one week more (recovery period) but anymore administration of the substances. The animals treated with B[a]P showed a weight increase after the first week of administration. The same phenomenon was observed in the lots combined with B[a]P and CEE (low and medium doses). The dose of 800 mg/kg of CEE showed similar values to the control group at the end of the treatment period. In the second part of the assay, when the substances were not administered, these experimental groups regained their normal weight. The dose of CEE (800 mg/kg) was not genotoxic nor cytotoxic. On the contrary, the B[a]P increases the frequency of micronucleated normochromatic erythrocytes (MNNE) and reduces the rate of polychromatic erythrocytes (PE) at the end of the treatment period. With respect to the combined lots, a significant decrease in the MN rate was observed from the sixth to the eighth day of treatment with the two high doses applied; the highest protection (60%) was obtained with 800 mg/kg of CEE. The same dose showed an anticytotoxic effect which corresponded to an improvement of 62.5% in relation to the animals administered with the B[a]P. In the second period, all groups reached values that have been seen in the control group animals. Our results suggest that the inhibition of clastogenicity of the cranberry ethanolic extract against B[a]P is related to the antioxidant capacity of the combination of phytochemicals present in its chemical composition.

Treatment of Bolivian Leishmania braziliensis Cutaneous and Mucosal Leishmaniasis.

Although infection with Leishmania braziliensis is perhaps the key reason to treat New World cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML), the total literature contains relatively few reported cases. With the aim of supplementing the meager clinical information available, we searched the records of Jorochito (Dermatology) Hospital, Bolivia, for the years 1999-2020 and identified treatment records for 1,696 naive CL patients and 355 naive ML patients. Because follow-up was poor for this real-world treatment experience in the developing world, only 255 CL patients (15%) and 114 ML patients (32%) attended follow-up at Hospital. We therefore engaged in an Active Search for "lost" patients, located a further 542 CL patients (32%) and 142 ML patients (44%), thus eventually accomplished follow up on 697 CL patients (41%) and 256 ML patients (72%). Granular adverse event data derived from hospital records is listed for the 902 CL and 86 ML patients administered Glucantime intramuscularly, the 401 CL and 202 ML patients administered Glucantime intravenously, and the 163 CL and 89 ML patients administered miltefosine orally. Efficacy was obtained from hospital records for patients seen at hospital and from patient recall communicated by telephone for the patients found in the Active Search. The overall CL cure rate was 508 of 697 CL patients (73%) with follow-up: intramuscular Glucantime-196/293 (67%); intravenous Glucantime-90/126 (71%); intralesional Glucantime-34/54 (63%); oral miltefosine-52/69 (75%). The overall ML cure rate was 161 of 256 ML patients (63%) with follow-up: intramuscular Glucantime-26/48 (54%); intravenous Glucantime-66/104 (63%); intravenous amphotericin B deoxycholate-19/35 (54%); oral miltefosine-50/71 (70%). We offer this extensive adverse event and efficacy experience as useful guides for clinicians presented with a L. braziliensis infection. The cure rates also illustrate the quandary of New World CL and ML chemotherapy: sufficiently high to be useful but nevertheless needing augmentation with new agents.

Inflammation, oxidative stress, and obesity.

Obesity is a chronic disease of multifactorial origin and can be defined as an increase in the accumulation of body fat. Adipose tissue is not only a triglyceride storage organ, but studies have shown the role of white adipose tissue as a producer of certain bioactive substances called adipokines. Among adipokines, we find some inflammatory functions, such as Interleukin-6 (IL-6); other adipokines entail the functions of regulating food intake, therefore exerting a direct effect on weight control. This is the case of leptin, which acts on the limbic system by stimulating dopamine uptake, creating a feeling of fullness. However, these adipokines induce the production of reactive oxygen species (ROS), generating a process known as oxidative stress (OS). Because adipose tissue is the organ that secretes adipokines and these in turn generate ROS, adipose tissue is considered an independent factor for the generation of systemic OS. There are several mechanisms by which obesity produces OS. The first of these is the mitochondrial and peroxisomal oxidation of fatty acids, which can produce ROS in oxidation reactions, while another mechanism is over-consumption of oxygen, which generates free radicals in the mitochondrial respiratory chain that is found coupled with oxidative phosphorylation in mitochondria. Lipid-rich diets are also capable of generating ROS because they can alter oxygen metabolism. Upon the increase of adipose tissue, the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), was found to be significantly diminished. Finally, high ROS production and the decrease in antioxidant capacity leads to various abnormalities, among which we find endothelial dysfunction, which is characterized by a reduction in the bioavailability of vasodilators, particularly nitric oxide (NO), and an increase in endothelium-derived contractile factors, favoring atherosclerotic disease.

Role of Kupffer cells in thioacetamide-induced cell cycle dysfunction.

It is well known that gadolinium chloride (GD) attenuates drug-induced hepatotoxicity by selectively inactivating Kupffer cells. In the present study the effect of GD in reference to cell cycle and postnecrotic liver regeneration induced by thioacetamide (TA) in rats was studied. Two months male rats, intraveously pretreated with a single dose of GD (0.1 mmol/Kg), were intraperitoneally injected with TA (6.6 mmol/Kg). Samples of blood and liver were obtained from rats at 0, 12, 24, 48, 72 and 96 h following TA intoxication. Parameters related to liver damage were determined in blood. In order to evaluate the mechanisms involved in the post-necrotic regenerative state, the levels of cyclin D and cyclin E as well as protein p27 and Proliferating Cell Nuclear Antigen (PCNA) were determined in liver extracts because of their roles in the control of cell cycle check-points. The results showed that GD significantly reduced the extent of necrosis. Noticeable changes were detected in the levels of cyclin D1, cyclin E, p27 and PCNA when compared to those induced by thioacetamide. Thus GD pre-treatment reduced TA-induced liver injury and accelerated the postnecrotic liver regeneration. These results demonstrate that Kupffer cells are involved in TA-induced liver and also in the postnecrotic proliferative liver states.

Detection of cytotoxic activity of lectin on human colon adenocarcinoma (Sw480) and epithelial cervical carcinoma (C33-A).

Lectins comprise a heterogeneous class of proteins that recognize the carbohydrate moieties of glycoconjugates with high specificity. Numerous studies have shown that lectins are capable of recognizing specific carbohydrate moieties displayed by malignant cells or tissues. The present work was performed to investigate the effects of tepary bean (Phaseolus acutifolius) lectins on proliferation, colony formation, and alteration of DNA synthesis of human malignant cells. Tepary bean lectin showed dose dependent  effects on the inhibition of viability as well as on colony formation in two human malignant cells lines (C33-A, Sw480); By contrast, tepary bean lectin only showed significant effects on DNA synthesis on Sw480 cells. Our results provide evidence of the anti- proliferative and cytotoxic effects of the tepary bean lectins on C33-A and Sw480 cells lines.

Case Report: COVID-19 Misdiagnosed as a Drug Reaction to Miltefosine.

We present case reports of two patients treated with miltefosine for mucocutaneous leishmaniasis whose gastrointestinal symptoms were initially diagnosed as a drug reaction and only later recognized as due to COVID-19. Gastrointestinal symptoms of COVID-19 are unusual, whereas gastrointestinal adverse drug reactions are very common. These reports exemplify that this infrequent presentation of COVID-19 is likely to be ascribed to a more common etiology such as a gastrointestinal drug reaction.

Exposure to sodium fluoride produces signs of apoptosis in rat leukocytes.

Fluoride is naturally present in the earth's crust and can be found in rocks, coal, and clay; thus, it can be found in small quantities in water, air, plants, and animals. Therefore, humans are exposed to fluoride through food, drinking water, and in the air they breathe. Flouride is essential to maintain bone strength and to protect against dental decay, but if it is absorbed too frequently, it can cause tooth decay, osteoporosis, and damage to kidneys, bones, nerves, and muscles. Therefore, the present work was aimed at determining the effect of intake of sodium fluoride (NaF) as an apoptosis inducer in leukocytes of rats treated for eight weeks with 1 or 50 parts per million (ppm) NaF. Expression of p53, bcl-2, and caspade-3 were used as apoptotic and general metabolism indicators of leukocyte-like indicators of the (INT) oxidation system. Male rats were exposed to NaF (1 and 500 ppm) for eight weeks, and then sacrificed weekly to obtain blood samples. Expression of p53, bcl-2, and caspase-3 were determined in leukocytes by Western blot, and general metabolism of leukocytes was analyzed with a commercial kit. We found changes in the expression of the proteins described, especially when the animals received 50 ppm of NaF. These results indicate that NaF intoxication can be an apoptosis inducer in rat leukocytes treated with the compound for eight weeks.

Effect of sodium fluoride ingestion on malondialdehyde concentration and the activity of antioxidant enzymes in rat erythrocytes.

Fluoride intoxication has been shown to produce diverse deleterious metabolic alterations within the cell. To determine the effects of sodium fluoride (NaF) treatment on malondialdehyde (MDA) levels and on the activity of antioxidant enzymes in rat erythrocytes, Male Wistar rats were treated with 50 ppm of NaF or were untreated as controls. Erythrocytes were obtained from rats sacrificed weekly for up to eight weeks and the concentration of MDA in erythrocyte membrane was determined. In addition, the activity of the enzymes superoxide, dismutase, catalase, and glutathione peroxidase were determined. Treatment with NaF produces an increase in the concentration of malondialdehyde in the erythrocyte membrane only after the eight weeks of treatment. On the other hand, antioxidant enzyme activity was observed to increase after the fourth week of NaF treatment. In conclusion, intake of NaF produces alterations in the erythrocyte of the male rat, which indicates induction of oxidative stress.

Mass Drug Administration of Triclabendazole for Fasciola Hepatica in Bolivia.

Human infection with Fasciola hepatica leads to obstruction of the common bile duct by adult worms and disease characterized by biliary colic, epigastric pain, and nausea. Recommended treatment is a single dose of triclabendazole (TCBZ) (10 mg/kg). Because in the 1990s the Bolivian Altiplano bordering Lake Titicaca was thought to have the highest prevalence of human fascioliasis worldwide, the Bolivian Ministry of Health instituted TCBZ mass drug administration (MDA). From 2008 to 2016 (excepting 2015), one dose of 250 mg was administered, usually in September/October, to each resident of highly endemic regions willing to participate. This is apparently the first reported use of MDA for Fasciola. The proportion of persons in key regions receiving TCBZ MDA was 87% in 2016. In 2017, we resurveyed key regions, and found that the MDA program had been dramatically successful. Whereas Fasciola prevalence was reported as 26.9% in Huacullani/Tiahuanaco and 12.6% in Batallas in 1999, there was 0.7% prevalence in Huacullani/Tiahuanaco and 1% in Batallas in 2017. However, lessons from schistosomiasis control efforts suggest that for sustained control of Fasciola infection, Fasciola MDA needs to be maintained and coupled with measures to control infection in the intermediary snail and in the animal hosts of F. hepatica.

Efficacy of miltefosine for Bolivian cutaneous leishmaniasis.

Oral miltefosine (2.5 mg/kg/d for 28 days) was compared with intramuscular antimony (20 mg/kg/d for 20 days) in the treatment of cutaneous leishmaniasis caused by Leishmania braziliensis in Palos Blancos, Bolivia. The cure rates with 6 months of follow-up were statistically similar: 36 of 41 evaluable miltefosine patients (88%) versus 15 of 16 (94%) evaluable antimony patients. However, antimony cured more rapidly, because, by 1 month after therapy, 31 of 44 miltefosine patients (70%) compared with 16 of 16 antimony patients (100%) had achieved cure. The two conclusions from this work are that oral miltefosine can be used for cutaneous disease in this part of Bolivia and that miltefosine was more effective for L. braziliensis in this region than for L. braziliensis in Guatemala. Chemotherapy needs to be evaluated in each endemic region, even if the "same" species of Leishmania causes disease in these locales.

Treatment of acute uncomplicated falciparum malaria with artemether-lumefantrine in nonimmune populations: a safety, efficacy, and pharmacokinetic study.

The efficacy and safety of artemether-lumefantrine for the treatment of malaria in nonimmune populations are not well defined. In this study, 165 nonimmune patients from Europe and non-malarious areas of Colombia with acute, uncomplicated falciparum malaria or mixed infection including P. falciparum were treated with the six-dose regimen of artemether-lumefantrine. The parasitologic cure rate at 28 days was 96.0% for the per protocol population (119/124 patients). Median times to parasite clearance and fever clearance were 41.5 and 36.8 hours, respectively. No patient had gametocytes after Day 7. Treatment was well tolerated; most adverse events were mild to moderate and seemed to be related to malaria. There were few serious adverse events, none of which were considered to be drug-related. No significant effects on ECG or laboratory parameters were observed. In conclusion, the six-dose regimen of artemether-lumefantrine was effective and well tolerated in the treatment of acute uncomplicated falciparum malaria in nonimmune patients.

Miltefosine Combined with Intralesional Pentamidine for Leishmania braziliensis Cutaneous Leishmaniasis in Bolivia.

Bolivian cutaneous leishmaniasis due to Leishmania braziliensis was treated with the combination of miltefosine (150 mg/day for 28 days) plus intralesional pentamidine (120 µg/mm2 lesion area on days 1, 3, and 5). Ninety-two per cent of 50 patients cured. Comparison to historic controls at our site suggests that the efficacy of the two drugs was additive. Adverse effects and cost were also additive. This combination may be attractive when a prime consideration is efficacy (e.g., in rescue therapy), avoidance of parenteral therapy, or the desire to treat locally and also provide systemic protection against parasite dissemination.

Harmonized clinical trial methodologies for localized cutaneous leishmaniasis and potential for extensive network with capacities for clinical evaluation.

INTRODUCTION: Progress with the treatment of cutaneous leishmaniasis (CL) has been hampered by inconsistent methodologies used to assess treatment effects. A sizable number of trials conducted over the years has generated only weak evidence backing current treatment recommendations, as shown by systematic reviews on old-world and new-world CL (OWCL and NWCL). MATERIALS AND METHODS: Using a previously published guidance paper on CL treatment trial methodology as the reference, consensus was sought on key parameters including core eligibility and outcome measures, among OWCL (7 countries, 10 trial sites) and NWCL (7 countries, 11 trial sites) during two separate meetings. RESULTS: Findings and level of consensus within and between OWCL and NWCL sites are presented and discussed. In addition, CL trial site characteristics and capacities are summarized. CONCLUSIONS: The consensus reached allows standardization of future clinical research across OWCL and NWCL sites. We encourage CL researchers to adopt and adapt as required the proposed parameters and outcomes in their future trials and provide feedback on their experience. The expertise afforded between the two sets of clinical sites provides the basis for a powerful consortium with potential for extensive, standardized assessment of interventions for CL and faster approval of candidate treatments.

Conducta sexual en jóvenes universitarios: Estudio de revisión / Sexual behavior in Ibero-American Youth: Review study

Resumen Objetivo: Describir y analizar estudios sobre la conducta sexual en jóvenes iberoamericanos. Método: Revisión bibliográfica de 150 referencias, tomadas de las bases de datos Web of Science, Latindex, Scopus, ProQuest, Redaly, Scielo, Ebsco. Se hizo análisis de calidad mediante el uso de la Herra- mienta de Evaluación de Métodos Mixtos (MMAT) para 91 artículos finales. Resultados: Existe bibliografía sobre las conductas sexuales del dominio corporal, poca del dominio social; la edad de inicio de la actividad sexual promedio en hombres fue de 15,8 años y 15,7 en mujeres. En los últimos diez años la edad de inicio de las relaciones sexuales se reduce en Chile (15,3), Colombia (16,95), España (17,97) y México (16,97); se mantiene relativamente estable en Portugal (17,25) y Ecuador (16,43); aumenta en Brasil (15,3); en Cuba (14,85) y Perú (14,77) es inestable. Conclusiones: Se plantea la necesidad de un abordaje orientado al disfrute del ejercicio de la sexualidad (hedonismo responsable) alejado del paradigma erotofóbico imperante. Se tiene como limitación el número de artículos por región; queda abierta la vía de replicar el estudio con una mayor muestra, además de explorar y generar datos sobre las conductas eróticas desde el modelo de dominio social-corporal de Parra-Villarroel y Pérez-Villegas.

Abstract Objective: Describe and analyze studies on sexual behavior in Ibero-American youngsters. Method: Bibliographic review of 150 references, taken from the databases Web of Science, Latindex, Scopus, ProQuest, Redaly, Scielo, Ebsco. Quality analysis was performed using the Mixed Methods Assessment Tool (MMAT) for 91 final articles. Results: There is bibliography on sexual behaviors of the corporal domain, little of the social domain; the average age of initiation of sexual activity in men was 15,8 years and 15,7 in women. Over the last ten years, the age of sexual debut has decreased in Chile (15,3), Colombia (16,95), Spain (17,97) and Mexico (16,97); it is relatively stable in Portugal (17,25) and Ecuador (16,43); it has increased in Brazil (15,3); in Cuba (14,85) and Peru (14,77) is unstable. Discussions: The need for an approach oriented to the enjoyment of the exercise of sexuality (respon- sible hedonism) away from the prevailing erotophobic paradigm is proposed. The limitation is the number of articles per region; the way is open to replicate the study with a larger sample, as well as to explore and generate data on erotic behaviors from the model of social bodily domains of Parra-Villarroel and Pérez-Villegas.