Mercury-induced aggregation of human lens γ-crystallins reveals a potential role in cataract disease.

Cataract disease results from non-amyloid aggregation of eye lens proteins and is the leading cause of blindness in the world. A variety of studies have implicated both essential and xenobiotic metals as potential etiological agents in cataract disease. Essential metal ions, such as copper and zinc, are known to induce the aggregation in vitro of human γD crystallin, one of the more abundant γ-crystallins in the core of the lens. In this study, we expand the investigation of metal-crystallin interactions to heavy metal ions, such as divalent lead, cadmium and mercury. The impact of these metal ions in the non-amyloid aggregation, protein folding and thermal stability of three homologous human lens γ-crystallins has been evaluated using turbidity assays, electron microscopy, electronic absorption and circular dichroism spectroscopies. Our results show that Hg(II) ions can induce the non-amyloid aggregation of human γC and γS crystallins, but not γD crystallin. The mechanism of Hg-induced aggregation involves direct metal-protein interactions, loss of thermal stability, partial unfolding of the N-terminal domain of these proteins, and formation of disulfide-bridged dimers. Putative Hg(II) binding sites in γ-crystallins involved in metal-induced aggregation are discussed. This study reveals that mercury ions can induce the aggregation of human lens proteins, uncovering a potential role of this heavy metal ion in the bioinorganic chemistry of cataract disease.

Postpartum consciousness disturbance: can covid-19 cause posterior reversible encephalopathy syndrome? / Alteración del nivel de conciencia puerperal: ¿puede el COVID-19 ser causa de síndrome de encefalopatía posterior reversible?

We describe the case of a 24-year-old pregnant woman with no history of note who was admitted with a diagnosis of bilateral pneumonia caused by the new coronavirus. Due to clinical worsening, she required urgent cesarean section with general anaesthesia and intubation for decubitus intolerance. After extubation, she presented altered mental state that required a differential diagnosis of encephalitis/meningitis secondary to SARS-CoV-2. CT and CT-angiography were normal, spinal fluid tests were non-specific, and magnetic resonance imaging reported posterior reversible encephalopathy syndrome (PRES) (due to radiological features suggestive of white matter vasogenic edema affecting the parietal, temporal and occipital lobes, along with altered mental state) secondary to gestational hypertension. Eleven days after the cesarean section the patient began to develop hypertension that required treatment. PRES is associated with certain clinical (headache, altered mental state, visual disturbances and convulsions) and radiological (reversible changes in white substance mainly affecting the parietal, temporal, and occipital lobes) characteristics suggestive of vasogenic oedema In pregnant SARS-CoV-2 patients, the differential diagnosis of hypertension and altered mental state is often extremely complicated because complementary tests can be normal and there is no immediate sign of peripartum hypertension. SARS-CoV-2 genome sequencing in spinal fluid could have provided a definitive diagnosis, but the treatment would not have differed.

Natural Enemies of the Harrisia Cactus Mealybug and Other Hypogeococcus Species (Hemiptera: Pseudococcidae) in Puerto Rico: Identification and Taxonomic Notes on Primary and Secondary Parasitoids.

Primary and secondary parasitoids of Hypogeococcus spp. (Hemiptera: Pseudococcidae) on Cactaceae, Amaranthaceae, and Portulacaceae were reported from field surveys conducted in Puerto Rico, USA, since 2009. Resident natural enemies of the Harrisia cactus mealybug (HCM), Hypogeococcus sp., which is devastating native cacti in Puerto Rico and threatening cacti in the adjacent Caribbean islands, were documented prior to the planned introductions of non-native biological control agents from South America against this pest. Two species of Encyrtidae (Hymenoptera: Chalcidoidea) were recorded as primary parasitoids of the HCM on Cactaceae: Leptomastidea hypogeococci Triapitsyn, which was the most common, and Anagyrus quilmes Triapitsyn, Logarzo & Aguirre. Another primary parasitoid, Acerophagus sp. near nubilipennis Dozier (Encyrtidae), was also reared from a different Hypogeococcus sp. on Amaranthaceae and Portulacaceae. Hyperparasitoids, usually via L. hypogeococci, included Prochiloneurus narendrani Noyes & Triapitsyn (Encyrtidae), Pachyneuron sp. (Hymenoptera: Pteromalidae), Chartocerus elongatus (Girault), and Chartocerus niger (Ashmead) (Hymenoptera: Signiphoridae). Cheiloneurus chrisiantorresi Triapitsyn sp. n. (Encyrtidae) is newly described and illustrated; its status as a suspect hyperparasitoid of Hypogeococcus sp. on Amaranthaceae and Portulacaceae, along with that of Cheiloneurus sp., will need to be verified. The recorded HCM predators include one species of Chamaemyiidae (Diptera), Leucopina bella (Loew), and three species of Coccinellidae (Coleoptera): Cryptolaemus montrouzieri Mulsant, Decadiomus austrinus (Gordon), and Scymnobius flavifrons (Melsheimer).

Survival after biochemical failure in prostate cancer treated with radiotherapy: Spanish Registry of Prostate Cancer (RECAP) database outcomes.

INTRODUCTION: The clinical course in patients with prostate cancer (PCa) after biochemical failure (BF) has received limited attention. This study analyzes survival time from recurrence, patterns of progression, and the efficacy of salvage therapies in patients treated with radical or postoperative radiotherapy (RT). METHODS: This is a multicenter retrospective comparative study of 1135 patients diagnosed with BF and treated with either radical (882) or postoperative (253) RT. Data correspond to the RECAP database. Clinical, tumor, and therapeutic characteristics were collected. Descriptive statistics, survival estimates, and comparisons of survival rates were calculated. RESULTS: Time to BF from initial treatment (RT or surgery) was higher in irradiated patients (51 vs 37 months). At a median follow-up of 102 months (14-254), the 8-year cause-specific survival (CSS) was 80.5%, without significant differences between the radical (80.1%) and postoperative (83.4%) RT groups. The 8-year metastasis-free survival rate was 57%. 173 patients (15%) died of PCa and 29 (2.5%) of a second cancer. No salvage therapy was given in 15% of pts. Only 5.5% of pts who underwent radical RT had local salvage treatment and 71% received androgen deprivation (AD) ± chemotherapy. The worst outcomes were in patients who developed metastases after BF (302 pts; 26.5%) and in cases with a Gleason > 7. CONCLUSIONS: In PCa treated with radiotherapy, median survival after BF is relatively long. In this sample, no differences in survival rates at 8-years have been found, regardless of the time of radiotherapy administered. AD was the most common treatment after BF. Metastases and high Gleason score are adverse variables. To our knowledge, this is the first study to compare outcomes after BF among patients treated with primary RT vs. those treated with postoperative RT and to evaluate recurrence patterns, treatments administered, and causes of death. The results allow avoiding overtreatment, improving quality of life, without negatively affecting survival.

The Ginkgo biloba extract (GbE) protects the kidney from damage produced by a single and low dose of carbon tetrachloride in adult male rats.

Gingko biloba leaves have been used as herbal medicine in China for 5000 years, and the standardized leaf extract (GB-STE) has some beneficial effects in the treatment of age-related, cardiovascular, and neurological diseases. The aim of this study was to investigate the renoprotective effects of the Gingko biloba extract (GbE) against the toxicity of a single and relatively low dose of carbon tetrachloride (CCl4). In male adult Wistar rats, we determined the urine flux, the concentration of total proteins in urine, the concentration of glucose in urine, and the concentration of malondialdehyde (MDA) in renal cortex as well as two markers of renal function (clearance of inulin and p-aminohippurate); we also compared the histological lesions caused by CCl4. Carbon tetrachloride increased the urinary concentration of total proteins, and the renal concentration of MDA; however, it did not modify the urine flux, urinary concentration of glucose, nor the inuline or the p-aminohipurate clearances. Morphologically, CCl4 generated some tubular damage that was more intense in the inner cortex of kidneys. The GbE extract counteracted the effects of CCl4 on the concentration of total proteins in urine, the concentration of renal MDA, and the renal histological changes. In conclusion the main toxic effects produced by CCl4 were prevented by the GbE, probably due to their antioxidant properties and the inhibition of the main P450 isoenzyme (CYP2E1) that metabolize CCl4.

The ATP levels in kidneys and blood are mainly decreased by acute ingestion of tullidora (Karwinskia humboldtiana).

Our previous acute toxicity studies with Karwinskia humboldtiana (Kh) in rats showed renal hemodynamic changes with a marked increase in the fractional excretion of sodium and morphological damage. To analyse the effects of Kh or 'tullidora' on energetic metabolism, a single dose of an oral preparation from the seed fruits was given to Wistar rats (1.25 g/kg). In tullidora-treated rats there was 8% mortality. ATP concentrations in renal tissue decreased significantly (control: 53.85+/-3.34, tullidora 38.28+/-5.31 micromol/g fresh tissue, P<0.05). Total blood (54.8+/-0.96, tullidora: 40.2+/-1.55 micromol/dL, P<0.01) and haemoglobin-ATP concentrations (3.69+/-0.12, tullidora: 2.56+/-0.11 micromol/g, P<0.01) were also significantly diminished. Moreover, the total protein in renal cortex from tullidora-treated rats decreased as compared to control group (control: 71.43+/-2.88, tullidora: 55.20+/-4.06 mg/g fresh tissue, P<0.05). In contrast, Na+-K+-ATPase activity in tullidora-treated animals was not different from control rats. These findings might partially explain the acute effects and mortality observed in the Kh treated rats.

[Antisynthetase syndrome without myositic disease: a case report]. / Síndrome antisintetasa sin afectación miosítica: a propósito de un caso.

Antisynthetase syndrome is a rare disorder, included among the idiopathic inflammatory myopathies, characterized by the presence of antisynthetase antibodies. We present a case of a patient with a suggestive clinical stage of interstitial lung disease, skin and articular disease, but without muscle involvement, with the presence of anti Jol antibodies.

Plasma levels of praziquantel decrease when dexamethasone is given simultaneously.

Treatment with praziquantel for neurocysticercosis frequently induces adverse reactions due to acute destruction of parasites; these reactions are suppressed by dexamethasone therapy. However, there is controversy about the most appropriate regimen with praziquantel and dexamethasone. We studied plasma levels of praziquantel in eight patients given the drug alone or with dexamethasone. Plasma levels of praziquantel were 50% lower in the same patient when dexamethasone was given simultaneously. Dexamethasone should not be added to praziquantel therapy as preventive treatment, but should be reserved for transient therapy of adverse reactions.

Immunosuppressive cyclolignans.

The immunosuppressive activity of several lactonic, nonlactonic, and heterocycle-fused cyclolignans has been demonstrated for the first time by use of a T-cell-mediated immune response. Of the compounds tested, 4'-demethyldeoxypodophyllotoxin (8), beta-apopicropodophyllin (6), and the isoxazoline-fused cyclolignan 15 are the most potent with respect to their suppression of activated splenocytes.

Glutathione S-transferases and esterases in placenta after normal and pre-eclamptic pregnancies.

Severe pre-eclampsia reduced significantly (P<0.05) by 68+/-6 per cent (mean+/-sem, n=10) the maximal velocity (V(max)) and, consequently, reduced significantly by 60+/-7 per cent the catalytic efficiency (C(E)) of placental glutathione transferase pi, assayed with ethacrynic acid. Mild and severe pre-eclampsia reduced significantly by 82+/-5 per cent (mean+/-sem, n=5) and by 41+/-5 per cent (mean+/-sem, n=10), respectively, the V(max)and, consequently, reduced significantly by 72+/-7 and by 33+/-13 per cent, respectively, the C(E)of esterase, assayed with p-nitrophenyl acetate. Furthermore, severe pre-eclampsia increased significantly by 296+/-78 per cent the Michaelis-Menten constant (K(m)) of total GST, assayed with chlorodinitrobenzene and, consequently, decreased significantly the C(E)by 83+/-3 per cent. On the other hand, the concentrations of total and non-protein thiols did not change significantly in placental homogenates from patients with mild or severe pre-eclampsia compared to normal pregnancies. These findings would indicate a decreased capacity of the glutathione transferases and esterase detoxification systems to protect the fetus from drugs prescribed to pregnant women suffering pre-eclampsia, mainly in the severe phase.

Histiocytic cytophagic panniculitis: a rare late complication of allogeneic bone marrow transplantation.

Histiocytic cytophagic panniculitis (HCP) is the name given to the hemophagocytic syndrome when subcutaneous fat is involved. Histologically, it is characterized by phagocytosis of blood elements by histiocytes that appear to be benign. We report this rare skin disease in a 46-year-old patient that occurred 32 months after an allogeneic bone marrow transplantation. This skin disease could be a manifestation of graft-versus-host disease, although the connection remains speculative.

Characterization of 3-carboxy-5-phosphono-1,2,3,4-tetrahydroisoquinoline (SC-48981), a potent competitive N-methy-D-aspartate (NMDA) receptor antagonist, in vitro and in vivo.

(+/-)-3-Carboxy-5-phosphono-1,2,3,4-tetrahydroisoquinoline (SC-48981), a conformationally restricted analog of the potent competitive N-methyl-D-aspartate (NMDA) antagonist, 2-amino-5-phosphonopentanoate (AP-5), potently inhibited the binding of [3H]glutamate to the N-methyl-D-aspartate (NMDA) receptors with a Ki of 1.6 mcM, but with minimal affinity for kaininate and quisqualate receptors (Ki greater than 50 mcM), in vitro. Consistent with its ability to antagonize the NMDA receptor, SC-48981 decreased the binding of [3H]glycine and [3H]TCP [1-(2-thienyl)cyclohexylpiperidine] to the NMDA-associated glycine and phencyclidine (PCP) recognition sites, in vitro. SC-48981 attenuated levels of basal cGMP and harmaline-induced increases in levels of cGMP in the mouse cerebellum, in vivo, in a competitive manner, with ED50 values of 5.5 and 8.7 mg/kg, i.p. Direct intracerebellar injection of SC-48981 (0.5 microgram) attenuated increases in levels of cGMP induced by central injection of the NMDA-associated glycine receptor agonist, D-serine and by NMDA itself. Parenteral administration of SC-48981 (25 mg/kg, s.c.) decreased basal levels of cGMP for up to 3 h. These results indicate that SC-48981 represents a novel bioavailable competitive NMDA antagonist with a long duration of action.

Sociomedical aspects of malaria control in Colombia.

A household interview survey combined with a serological survey on the incidence of malaria attacks and prevalence of antibodies has been carried out in rural and urban areas of the pacific coast of Colombia. Additional information on people's knowledge, attitudes and behaviour towards malaria was collected by means of participant observation and informal interviews. The results show that people incorporate modern and traditional elements into their concepts of the disease and treatment strategies. The deficiencies of the official control programmes are shown from the people's point of view. Some human factors which influence malaria transmission are discussed and an estimate of the accuracy of self-diagnosis presented.

Serotypes of Escherichia coli isolated from septicaemic chickens in Galicia (northwest Spain).

The purpose of this study was to establish the serogroups of Escherichia coli that cause avian colibacillosis in Spain. The serogroups of 625 avian E. coli isolated between 1992 and 1993 were determined. The 458 E. coli from chickens with septicaemia belonged to 62 different O serogroups; however, 59% were of one of 18 serogroups (O1, O2, O5, O8, O12, O14, O15, O18, O20, O53, O78, O81, O83, O102, O103, O115, O116 and O132). These 18 serogroups were also determined as an important percentage (29%) of control isolates from faeces of healthy birds. Nevertheless, a significant difference (59% versus 29%; P < 0.001) was observed. Furthermore, the serogroups O12, O14, O18, O53, O78, O81, O102, O115, O116 and O132 were almost exclusively identified among septicaemic E. coli (31% versus 3%; P < 0.001). The high prevalence of O18, O81, O115, O116 and O132 isolates was not expected and may indicate the emergence of five new serogroups associated with avian colibacillosis not yet reported.

Synthesis and antineoplastic activity of cyclolignan aldehydes.

Several aldehydes related to methyl 9-deoxy-9-oxo-alpha-apopicropodophyllate, a selective antitumour agent against the HT-29 colon carcinoma, have been prepared and evaluated for their cytotoxic activities on four neoplastic cell lines (P-388, A-549, HT-29 and MEL-28). All of them lacked the lactone ring but maintained their cytotoxicity at, or under, the microM level.

Pathologic rupture of the spleen during induction with ATRA in a patient with acute promyelocytic leukemia.

Pathological rupture of the spleen is a rare but well recognized complication in hematological malignancies. Early clinical recognition of this life-threatening complication is necessary for rapid intervention. Here, we report on the case of a 26-year-old woman with acute promyelocytic leukemia who presented rupture of the spleen on day +2 of treatment with ATRA plus idarrubicin. In patients with acute leukemia, the presence of a painful abdomen and a sudden drop in hemoglobin levels, should alert of a possible splenic rupture, even without additional symptoms. This would facilitate an early treatment intervention with no modification to the chemotherapy schedule.

[The reform process and social participation in health in Latin America]. / Los procesos de reforma y la participación social en saluden América Latina.

Currently, many countries throughout the world are reforming their health services. Even though these reforms differ according to the country's characteristics, they share many policies, one of which is the promotion of social participation in health-related matters. This policy, however, is not new in the field of health service organization. Throughout the last century, individual or collective collaboration between the population and health services has been promoted by several philosophies and concepts with different aims: from the search for collaboration with the general public to broaden public health system coverage to the promotion of the creation of mechanisms that would allow society to exercise control over these services' performance. Nevertheless, for the public to be involved with these services, several factors concerning both the services themselves and the population, need to converge. Although the theoretical frameworks that have encouraged social participation throughout the history of the development of health systems differ considerably, their practical implementation shares many common elements in all periods, from participation as a means of obtaining certain objectives to being an end in itself, as a democratic process. This can also be applied to the current promotion of social participation policies in the context of health care reforms, which are analyzed using Colombia and Brazil as examples.

[The first operations performed with chloroform in Spain. More facts and new contributions]. / Las primeras operaciones efectuadas con el cloroformo en España. Más datos y nuevas aportaciones.

Although the issue of clinical introduction of chloroform in Spain was rather controversial, we can assure now with no doubt that first news of its discovery reached our country by the end of November and beginning of December of 1847. The cities first receiving those first news were Cádiz, Madrid, Barcelona, and Santiago de Compostela; in the latter two cities, during the first days of December, the new anesthetic agent was already available and the first experiments on dogs were conducted in 19th Sunday and first clinical assays in Barcelona and in Santiago de Compostela, the first experiments in Spain, were carried out in December 20th. Spanish scientific and daily press, particularly, press of Barcelona and Madrid promptly reflected the events and informed their readers about the discovery of chloroform as anesthetic. Our research deals with some of these aspects and we believe that will contribute to clarify not fully studied points to date.

[Design of an expert system for decision-making in an emergency situation]. / Diseño de un sistema experto para toma de decisiones en situación de urgencia.

OBJECTIVES: To study the clinical applicability of the expert system URGSANT as a help in making up decisions in emergencies. MATERIAL AND METHODS: URGSANT is an expert system implemented in INSIGT 2+ which is structured in a modular and hierarchical form. It contemplates 44 urgent situations relating to the central nervous system, hematopoietic, cardiovascular, respiratory, gastrointestinal, genitourinary, endocrinological, and miscellaneous group. Validation of the program was made by four anesthesiologists who evaluated the performance of the program in 25 emergency cases and in 25 other situations that were treated by other specialists. RESULTS: The rationale of the system was basically correct. In most cases the program was considered efficient or very efficient during the different clinical situations and only in one case its guidance was wrong. CONCLUSIONS: The URGSANT expert system is an efficient and useful method for the clinician during emergency situations.