SARS-CoV-2 host tropism: An in silico analysis of the main cellular factors.

Recent reports have shown that small and big felines could be infected by SARS-CoV-2, while other animals, like swines and mice, are apparently not susceptible to this infection. These findings raise the question of the role of cell factors associated with early stages of the viral infection in host selectivity. The cellular receptor for SARS-CoV-2 is the Angiotensin Converting Enzyme (ACE2). Transmembrane protease serine 2 (TMPRSS2) has been shown to prime the viral spike for its interaction with its receptor. GRP78 has also been proposed as a possible co-receptor. In this study, we used several bioinformatics approaches to bring clues in the interaction of ACE2, TMPRSS2, and GRP78 with SARS-CoV-2. We selected several mammalian hosts that could play a key role in viral spread by acting as secondary hosts (cats, dogs, pigs, mice, and ferrets) and evaluated their predicted permissiveness by in silico analysis. Results showed that ionic pairs (salt bridges, N-O pair, and long-range interactions) produced between ACE2 and the viral spike has an essential function in the host interaction. On the other hand, TMPRSS2 and GRP78 are proteins with high homology in all the evaluated hosts. Thus, these proteins do not seem to play a role in host selectivity, suggesting that other factors may play a role in the non-permissivity in some of these hosts. These proteins represent however interesting cell targets that could be explored in order to control the virus replication in humans and in the intermediary hosts.

[Maternal serum 25-hydroxy vitamin D levels in the first trimester and adverse gestational outcomes]. / Concentraciones séricas maternas de 25-hidroxivitamina D en el primer trimestre y resultados adversos gestacionales.

BACKGROUND: Some disorders of pregnancy and newborn have been associated with vitamin D deficiency (25 (OH) D) in maternal serum. The pathophysiology of this relationship is unknown today. OBJECTIVE: The aim of this study was to determine whether serum levels of vitamin D at the beginning of pregnancy are associated with gestational diabetes, hypertensive disorders of pregnancy, preterm birth and fetal growth restriction. MATERIAL AND METHOD: We conducted a prospective cohort study in 370 pregnant women at low obstetric risk randomly selected in our area (latitude 42 ° 20'N). The level of 25-hydroxy vitamin D was determinate between 8 and 14 weeks of pregnancy. We studied the relationship between the status of vitamin D and gestational diabetes, preeclampsia, preterm birth, intrauterine growth restriction and small for gestational age. The statistic analysis was performed using SPSS 15.0 and 3.1 Epidat programs. RESULTS: The prevalence of vitamin D deficiency in pregnant women in this serie was 96.8%, 34.6% had severe deficiency. After adjusting for maternal and seasonal variables, we haven't found association between first trimester maternal serum vitamin D levels and pregnancy outcomes studied. CONCLUSIONS: The pregnancy outcome was independent of the first trimester maternal serum 25(OH)D status.

Presence of a thapsigargin-sensitive calcium pump in Trypanosoma evansi: Immunological, physiological, molecular and structural evidences.

In higher eukaryotes, the sarco-endoplasmic reticulum (ER) Ca(2+)-ATPase (SERCA) is characterized for its high sensitivity to low concentrations of thapsigargin (TG), a very specific inhibitor. In contrast, SERCA-like enzymes with different sensitivities to TG have been reported in trypanosomatids. Here, we characterized a SERCA-like enzyme from Trypanosoma evansi and evaluated its interaction with TG. Confocal fluorescence microscopy using BODIPY FL TG and specific anti-SERCA antibodies localized the T. evansi SERCA-like enzyme in the ER and confirmed its direct interaction with TG. Moreover, the use of either 1 µM TG or 25 µM 2',5'-di (tert-butyl)-1,4-benzohydroquinone prevented the reuptake of Ca(2+) and consequently produced a small increase in the parasite cytosolic calcium concentration in a calcium-free medium, which was released from the ER pool. A 3035 bp-sequence coding for a protein with an estimated molecular mass of 110.2 kDa was cloned from T. evansi. The corresponding gene product contained all the invariant residues and conserved motifs found in other P-type ATPases but lacked the calmodulin binding site. Modeling of the three-dimensional structure of the parasite enzyme revealed that the amino acid changes found in the TG-SERCA binding pocket do not compromise the interaction between the enzyme and the inhibitor. Therefore, we concluded that T. evansi possesses a SERCA-like protein that is inhibited by TG.

Setting up an emergency stock for metabolic diseases.

INTRODUCTION: Therapeutic management of inborn errors of metabolism (IEMs) is complicated. The drugs involved are classified as orphan, and their supply depends on whether they are orphan medicines, investigational drugs, or need to be prepared as a compounded formula. MATERIALS AND METHODS: We analyzed emergency criteria, availability, and permanent location of metabolic drugs within the hospital. Information on therapeutic usage, administration, and dosage was also recorded. RESULTS: A stock for treating IEMs should include chelating agents, drugs to treat deficiencies, enzyme supplements, and other specific treatments. Hyperammonemia was considered to be life-threatening; therefore, an emergency supply of drugs to treat this condition should be kept permanently in the hospitalization unit. CONCLUSIONS: Emergency drug stocks are highly recommended in tertiary hospitals in order to improve care for patients susceptible to IEM.

Cervical scrapes levels of insulin-like growth factor-II and insulin-like growth factor binding protein 3 in women with squamous intraepithelial lesions and cervical cancer.

A growing number of studies have demonstrated an association between serum levels of insulin-like growth factors (IGFs) and IGF binding protein-3 (IGFBP-3) and increased risk for various cancers. The aim of this study was to evaluate the relationship between levels of IGF-II or IGFBP-3 in cervical scrapes with cervical cancer and precancerous lesions: low-grade squamous intraepithelial lesion (LSIL) and high-grade squamous intraepithelial lesion (HSIL). 4 groups of cases were examined: LSIL (n=20), HSIL (n=28), cervical cancer (n=45), and controls (n=51). Control subjects were women with normal, HPV DNA-negative Papanicolau (Pap) test. IGF-II and IGFBP-3 levels in cervical scrapes were measured by ELISA. Results show that median protein levels of IGF-II were significantly lower in cervical cancer cases vs. controls (446.5 ng/mg vs. 1,168.6 ng/mg, p<0.001). Significantly higher values of IGFBP-3 were found in HSIL vs. controls (median: 549.5 ng/mg vs. 216 ng/mg; p=0.018), and were not affected by HR HPV infection, meanwhile no significant differences were observed in IGFBP-3 levels between LSIL or cervical cancer as compared to controls. These data suggests that the progression to cervical cancer is associated with alterations in the IGF system and not affected by HR HPV infection. More studies are needed to understand the possible role of IGFBP-3 in cervical carcinogenesis.

Cutaneous metastases of hepatocellular carcinoma.

Cutaneous metastases are an unusual finding that may present as the first sign of an internal neoplasia. A case of cutaneous metastases of hepatocellular carcinoma, which may often involve other organs but very rarely metastases to the skin, is reported.

[Intravenous remifentanyl for labor analgesia]. / Remifentanilo intravenoso para analgesia del trabajo del parto.

BACKGROUND: Intravenous remifentanil may be the preferred analgesic when regional techniques are contraindicated. OBJECTIVE: To perform a systematic review on the use of remifentanil for analgesia in labor. METHODS: We searched MEDLINE (January 1995-August 2007) for studies on obstetric analgesia with remifentanil. RESULTS: We found 32 references representing the use of remifentanil in 257 women in labor. In most cases, patients reported relief of pain and a high level of satisfaction, with no severe side effects in mothers or neonates. When compared with meperidine and nitrous oxide in clinical trials, remifentanil provided better analgesia with fewer adverse effects. CONCLUSION: Analgesia with intravenous remifentanil is more effective and safer than other alternatives to regional analgesic techniques in obstetrics. Nevertheless, the optimum system for infusing the drug must b e established and further studies of maternal and fetal safety should be carried out.

Remifentanilo intravenoso para analgesia del trabajo del parto / Intravenous remifentanyl for labor analgesia

La analgesia con remifentanilo intravenoso podría serla primera alternativa a las técnicas regionales cuandoéstas se encuentran contraindicadas.OBJETIVO: Revisión sistemática de la bibliografía disponiblesobre el uso de remifentanilo como analgesia delparto. Método: Búsqueda en MEDLINE (enero 1995-marzo 2009) y revisión de bibliografía de las publicacionessobre la analgesia obstétrica con remifentanilo.RESULTADOS: Se encontraron 37 referencias con untotal de 281 embarazadas tratadas con remifentanilo. Enla mayoría de los casos las pacientes mostraron descensoen el dolor referido y alto grado de satisfacción, sinefectos secundarios graves en las madres o neonatos.Comparándolo en ensayos clínicos con meperidina y óxidonitroso, el remifentanilo obtuvo mejores resultados enanalgesia y menores efectos secundarios.CONCLUSIÓN: La analgesia con remifentanilo intravenosoes una alternativa más eficaz y segura que otras técnicasno regionales en la analgesia obstétrica. Aún debeestablecerse el sistema óptimo de administración y se precisanestudios más amplios de seguridad materno-fetal(AU)

BACKGROUND: Intravenous remifentanil may be the preferredanalgesic when regional techniques are contraindicated.OBJETIVE: To perform a systematic review on the use ofremifentanil for analgesia in labor.METHODS: We searched MEDLINE (January 1995-August 2007) for studies on obstetric analgesia withremifentanil.RESULTS: We found 32 references representing the use ofremifentanil in 257 women in labor. In most cases, patientsreported relief of pain and a high level of satisfaction, with nosevere side effects in mothers or neonates. When compared withmeperidine and nitrous oxide in clinical trials, remifentanilprovided better analgesia with fewer adverse effects.CONCLUSION: Analgesia with intravenous remifentanil ismore effective and safer than other alternatives to regionalanalgesic techniques in obstetrics. Nevertheless, the optimumsystem for infusing the drug must be established and furtherstudies of maternal and fetal safety should be carried out(AU)

Differential expression of IGF-I and insulin receptor isoforms in HPV positive and negative human cervical cancer cell lines.

Human papillomavirus (HPV) is the main risk factor for cervical cancer; however, some carcinomas occur in the absence of the virus. IGF-IR and an isoform of the insulin receptor, IR-A, play important roles in cancer. In this study we assessed the role of the IGF/insulin receptors in cervical cancer cell lines with different HPV status, SiHa (HPV positive), and C33a (HPV negative). Different patterns of receptor expression were found; while SiHa expressed IGF-IR, IR-A and IR-B, and IR/IGF-IR hybrid receptors, C33a cells expressed the IR-A only. Tyrosine phosphorylation of these receptors in response to their corresponding ligands correlated with the expression level of these receptors in the cell lines. Activation of PI3-K and MAPK pathways was revealed in both cell lines, however, no effects on proliferation, migration, or invasion were observed. Here we show that cervical cancer cell lines--positive and negative for HPV--differ in the type of insulin and IGF-1 receptors expressed. Additional studies are needed for characterization of the role of IR-A in cervical carcinogenesis.

[Iron deficiency: not always blood losses]. / Ferropenia: no siempre son pérdidas.

UNLABELLED: Iron deficiency may be the only presenting sign of malabsorption due to the presence of intestinal villous atrophy. Once gastrointestinal blood losses have been excluded, intestinal malabsorption should be investigated. OBJECTIVES: To determine the utility of jejunal biopsy in the evaluation of iron deficiency due to a defective absorption and the different diseases that may cause malabsortive iron deficiency. METHODS: Seventy patients with iron deficiency (ferritin<25 ng/ml), referred to the Unitat de Proves Funcionals Digestives to perform a jejunal biopsy were included. Jejunal biopsy was obtained distal to Treitz with a Watson capsule. Histological changes were classified according to the criteria proposed by Marsh. RESULTS: Jejunal biopsy was performed in 66 patients. Histology was normal in 25, unespecific in 1, showed inflammatory infiltrate in 12, hyperplastic changes in 2 and atrophy in 25. In one patient showed intestinal giardiasis. The clinical diagnosis was celiac sprue in 21 patients (32%), aclorhydria in 7 (10.5%), bacterial overgrowth in 1 (1.5%), intestinal giardiasis in 1 (1.5%), menstrual blood loss in 1 (1.5%) and 35(53%) patients remained without a definitive diagnosis. CONCLUSIONS: Jejunal biopsy is useful in the evaluation of iron deficiency due to intestinal malabsorption and reveals intestinal abnormalities in a significant number of cases.

Ferropenia: no siempre son pérdidas / Iron deficiency: not always blood losses

La ferropenia puede ser la única manifestación de un síndrome malabsortivo, secundario a la presencia de una atrofia intestinal. Por ello, descartadas las pérdidas gastrointestinales, debería tenerse en cuenta esta posibilidad en el estudio de la ferropenia. Objetivos: Evaluar la utilidad de la biopsia yeyunal en el diagnóstico de la malabsorción intestinal como causa de ferropenia y analizar cuales son las causas de ferropenia malabsortiva. Método: Se han incluido 70 pacientes con ferropenia (ferritina < 25 ng/ml) remitidos a la Unitat de Proves Funcionals Digestives, para la valoración de una posible malabsorción intestinal mediante la realización de una biopsia yeyunal. La biopsia yeyunal se obtuvo distal al ángulo de Treitz mediante cápsula de Watson. Se clasificaron los resultados histológicos según los criterios de Marsh. Resultados: La biopsia yeyunal se realizó en 66 pacientes. Fue normal en 25 pacientes, inespecífica en 1, en 12 se evidenciaron lesiones grado 1 (infiltrado linfocitario), en 2 lesiones grado 2 (hiperplasia de criptas) y en 25 lesiones grado 3 (atrofia). En otro paciente se objetivó una giardiasis intestinal. El diagnóstico clínico de los pacientes incluídos fue de enfermedad celíaca en 21 (32 por ciento), aclorhidria en 7 (10,5 por ciento), sobrecrecimiento bacteriano en 1 (1,5 por ciento), giardiasis intestinal en otro (1,5 por ciento), pérdidas ginecológicas en otra (1,5 por ciento) y 35 (53 por ciento) quedaron sin diagnóstico definitivo. Conclusiones: La biopsia yeyunal es una prueba útil en el diagnóstico de malabsorción como causa de ferropenia, permitiendo poner de manifiesto la existencia de patología intestinal en un alto porcentaje de casos (AU)

Systematic genetic study of Alzheimer disease in Latin America: mutation frequencies of the amyloid beta precursor protein and presenilin genes in Colombia.

Nearly all mutations in the presenilin 1 (PSEN1), presenilin 2 (PSEN2), and amyloid beta precursor protein (APP) genes lead to early-onset Alzheimer disease (EOAD, onset age at or before 65 years). In order to assess the genetic contribution of these genes in a series of Colombian AD cases, we performed a systematic mutation analysis in 11 autosomal dominant, 23 familial, and 42 sporadic AD patients (34% with age of onset < or = 65 years). No APP missense mutations were identified. In three autosomal dominant cases (27.2%), two different PSEN1 missense mutations were identified. Both PSEN1 mutations are missense mutations that occurred in early-onset autosomal AD cases: an I143T mutation in one case (onset age 30 years) and an E280A mutation in two other cases (onset ages 35 and 42 years). In addition, a novel PSEN1 V94M mutation was present in one early-onset AD case without known family history (onset age 53 years) and absent in 53 controls. The E318G polymorphism was present in five AD cases and absent in controls. In PSEN2, two different silent mutations were detected, including one not reported elsewhere (P129). The majority of the Colombian AD cases, predominantly late-onset, were negative for PSEN and APP mutations.

[Paraquat poisoning: report of two cases and literature review]. / Intoxicación por paraquat: presentación de dos casos y revisión de la literatura.

Cases of poisoning with pesticides, especially suicidal ones, continue to be an important therapeutic problem. The heribicide paraquat (1.1' dimethyl-4.4' bipyridylium dichloride) is the second cause of pesticide poisoning in our country, which is associated with a high mortality rate. We report two cases of suicidal ingestion of paraquat who developed multiorgan failure with a lethal outcome. We also present a brief review of the literature, mainly focused on the different therapeutic options.

APOE epsilon4 and Alzheimer's disease: positive association in a Colombian clinical series and review of the Latin-American studies.

OBJECTIVE: As the strength of the association between the APOE epsilon4 allele and Alzheimer's disease (AD) varies across ethnic groups, we studied if there was such an association in Colombian patients. METHOD: We performed apolipoprotein E (APOE) genotyping in a clinical sample of 83 unrelated AD patients, predominantly late-onset (>65 yrs) including familial ( n =30) and sporadic AD cases (n= 53) diagnosed according to NINCDS-ADRDA criteria and assessed by a multi-disciplinary team. Control subjects (n = 44) had no significant cognitive impairment by medical interview and neuro-psychological testing. RESULTS: We found a high association (OR= 5.1 95%CI 1.9 -13.6) between APOE epsilon4 and AD, in this series with predominantly late-onset cases with familial aggregation in 24 cases (28.9%). A significant negative association was found between epsilon2 and AD (OR= 0.2 95% CI 0.05-0.75). CONCLUSION: Further population-based surveys in Colombia are warranted to precise a possible dose effect of APOE epsilon4.

A comparison of 0.0625% bupivacaine with fentanyl and 0.1% ropivacaine with fentanyl for continuous epidural labor analgesia.

UNLABELLED: We compared the analgesic efficacy and the degree of motor block achieved with epidural infusion of 0.0625% bupivacaine (Group B) versus 0.1% ropivacaine (Group R), both with 0.0002% fentanyl (2 microg/mL) in laboring patients. A prospective, double-blinded study was performed in 98 ASA physical status I-II parturients who were divided randomly into two groups to receive either bupivacaine or ropivacaine after catheter location had been tested with an initial bolus of lidocaine and fentanyl. The infusion rate was 15 mL/h in every case. When pain was perceived, 5-mL boluses of the assigned epidural analgesic were administered every 10 min until analgesia was achieved. We recorded pain intensity, level of sensory block, degree of motor block, hemodynamic variables, secondary effects, mode of delivery, neonatal outcome, and patient satisfaction. There were no statistically significant differences in any of the factors analyzed. Highly effective analgesia was achieved in both groups with a small incidence of motor block. These findings suggest that bupivacaine may be more potent than ropivacaine. IMPLICATIONS: We compared different concentrations of epidural bupivacaine and ropivacaine thought to be equipotent. Both solutions were equally efficient in providing highly effective epidural analgesia for labor with minimal motor block. These findings suggest that bupivacaine may be more potent than ropivacaine.

Coordination chemistry of co(II)-bleomycin: its investigation through NMR and molecular dynamics.

Previous studies on the coordination chemistry of Co-bleomycin have suggested the secondary amine in beta-aminoalanine, the N5 and N1 nitrogens in the pyrimidine and imidazole rings, respectively, and the amide nitrogen in beta-hydroxyhistidine as equatorial ligands to the cobalt ion. The primary amine in beta-aminoalanine and the carbamoyl group of the mannose have been proposed alternatively as possible axial ligands. The first coordination sphere of Co(II) in Co(II)BLM has been investigated in the present study through the use of NMR and molecular dynamics calculations. The data collected from the NMR experiments are in agreement with the equatorial ligands previously proposed, and also support the participation of the primary amine as an axial ligand. The paramagnetic shifts of the gulose and mannose protons could suggest the latter as a second axial ligand. This possibility was investigated by way of molecular dynamics, with distance restraints derived from the relaxation times measured through NMR. The molecular dynamics results indicate that the most favorable structure is six-coordinate, with the primary amine and either the carbamoyl oxygen or a solvent molecule occupying the axial sites. The analysis of the structures previously derived for HOO-Co(III)-bleomycin and HOO-Co(III)-pepleomycin led us to propose the six-coordinate structure with only endogenous ligands, as the one held in solution by the Co(II) derivative of bleomycin.

[Extracorporeal respiratory assistance (ECRA): initial experiences in Spain]. / Asistencia respiratoria extracorpórea (AREC): primeras experiencias en España.

UNLABELLED: The attendance respiratory extracorporeal (AREC) is an oxygenation form for membrane extracorporeal with flow tidal and veno-venous cannula described by Chevalier et al. in 1990. We present our clinical experience so much with AREC in system veno-venous flow tidal as veno-arterial. From october of 1997 until the present time we have treated three patients by means AREC, in two patients with veno-venous system and in one veno-arterial. In all the cases bomb Collin-Cardio has been used with bladder for flow tidal and membrane of oxygenation of 0.8 m2, being inserted a system of alternative clamp of the branches of the circuit. The system AREC has been used in two patients with congenial diaphragmatic hernia, right in a case and left in the other one. The gestational age was of 38 and 36 weeks with a weight of 3,200 and 2,900 grams. Both patients were remitted from other centers by failure of the conventional treatment. In both cases the indication of AREC was the sharp deterioration of the general state with failure of the conservative treatment, being the previous oxygenation index of 109 and 112. The third patient precised veno-arterial AREC for ventricular failure during the correction of the congenital heart disease, this patient was 5 month old and the weight was 5,000 grams. The duration of AREC in the cases of congenital diaphragmatic hernia was of 14 and 10 days. In a patient the diaphragmatic hernia was corrected at the 55 hours of being in AREC. In the second case the hernia had been surgical corrected in another center. The exit of AREC in both cases carries out after a discreet improvement of the lung function. Both patients died at the 24 and 48 hours of the decannulation for cerebral hemorrhage and respiratory failure. The third patient stayed stable in veno-arterial AREC during 4 days, with hemodynamic support of 130 ml/kg/min, retiring the support to present absence of cerebral activity. CONCLUSIONS: With the derived limitations of the extreme severity of the treated cases and the current phase of beginning of the AREC team, we think that it is a useful and available technique in our country, for the handling of patient with cardiorespiratory failure while waiting for improvement of their base pathology.

[Wallenberg syndrome in childhood secondary to the striking by lightening]. / Síndrome de Wallenberg en la infancia secundario a electrofulguración.

Wallenberg's Syndrome (WS) is exceptional in childhood. We present a case of a 10 year-old girl with a WS caused by an embolism in the right lateral portion of the medulla secondary to an electrofulguration, but with an unusual progressive outcome, developing clinical signs of medial medullar injury, leading even into a respiratory failure 30 days after admittance. She only became stable after surgical lesion decompression. There was no evidence of vascular malformation, finding only a great oedema. The pathology only showed changes compatible with brain infarction. This case makes again clear the superiority of MRI upon CT-scan to diagnose a WS. We think that the unusual progression of the lesion was due to great medullar oedema found on surgery, involving the brain regional flow.

[Addition of ritanserin to the treatment with propranolol in cirrhotic patients: effects on portal pressure]. / Adición de ritanserina al tratamiento con propranolol en enfermos cirróticos: efectos sobre la presión portal.

The use of vasodilators to prevent the rupture of esophagic varices (EV) due to portal hypertension (PH) would reduce the portal pressure (PP) as the result of increased portocolateral flow. Rinsaterine, a 5-HT2 receptor blocker, reduces PP in experimental models of PH. This pilot study was designed to verify if ritanserine has a sustained and additive effect to propranolol on PP in cirrhotic patients with PH. Ten chronic patients with EV, under prophylactic therapy with propranolol and with a suprahepatic venous pressure gradient (SVPG) > 12 mm Hg, received ritanserine (0.11-0.14 mg/kg/day). One patients completed one month of treatment due to drug intolerance. Nine patients completed one month of treatment; SVPG did not show any significant variation in four patients and decreased 3 mm Hg in five patients, which were treated during 70 days more. After then, HVPG returned to its previous values except in one patient. The long-term association between ritanserine and propranolol does not improve the results of propranolol. However, the initial response observed in all of these patients supports the role of the serotoninergic system in the PH and states the need for further studies on 5-HT2 blocking for the prophylaxis of EV rupture.