The influence of age, period, and cohort factors on the incidence of kidney cancer in Spain 1990-2019: Evidence from the global burden of disease study.

OBJECTIVE: This study aimed to assess the influence of age, period, and cohort (A-P-C) factors on kidney cancer (KC) incidence trends in Spain from 1990 to 2019. METHODS: Employing data from the Global Burden of Disease Study 2019, we employed joinpoint analysis to determine long-term patterns and A-P-C modelling to quantify net drift, local drift, longitudinal age curves, and rate ratios (RRs) of period and cohort effects. RESULTS: Over the period 1990-2019, an estimated 142,811 cases of KC were diagnosed in Spain. A consistent upward trend in KC incidence was observed for both men and women, with the male-to-female ratio remaining stable at 2.6. Joinpoint analysis identified three distinct periods for men: An initial period (1990-1995) characterised by a significant increase in rates, a subsequent period (1995-2016) characterised by a slowdown in the rate of increase, and a final period (2016-2019) in which rates have plateaued. In women, 2 time periods were observed: an initial period (1990-2007) in which rates increased significantly, followed by a period of stabilization (2007-2019). Men born in the early-mid 20th century had a rising KC risk, peaking in the 1960s. Women's risk rose steadily, peaking in the late 1990s. CONCLUSION: A-P-C analysis reveals steady KC incidence increase in both genders over three decades. This highlights the need for targeted public health policies and effective prevention strategies.

Bladder cancer mortality trends in Spain: 1980-2021.

OBJECTIVE: We propose to update bladder cancer mortality rates in Spain from 1980 to 2021, by sex and age-group, by autonomous community (AC). MATERIALS AND METHODS: The public online databases of the National Statistical Institute were used to obtain data on population and bladder cancer mortality. Age-standardised mortality rates (ASMRs), all ages and truncated (<75 and ≥75) were estimated and reported as rates per 100,000 persons. Joinpoint regression software was used for estimation and trend analysis of ASMRs bladder cancer. RESULTS: In the last decade, the ASMR for bladder cancer (all ages, <75 years and ≥75 years) decreased significantly in Spain for both sexes. This trend was observed in 12 ACs for men and in 4 ACs (Andalusia, Canary Islands, Catalonia and Madrid) for women, although to different degrees. For men, ASMR remained stable in Castilla-León and La Rioja (<75 years), Cantabria, Castilla-La Mancha and Valencia (≥75 years) and the 2 Castilian regions (all ages). For women, ASMR also decreased in Valencia (<75 and ≥75), Castilla-León (≥75), Galicia (≥75 and all ages) and Navarre (<75 and all ages). CONCLUSION: Our results reveal significant variations in trends by AC, sex and age group, emphasizing the need for continued follow-up and targeted interventions to further reduce bladder cancer mortality rates in Spain.

A linear-polymer-based lactoferrin-selective recognition element for an ELISA mimic: A proof of concept.

The synthesis of polymers with tailored properties for the recognition of macromolecules such as proteins is challenging. In this work, the synthesis of a new polymer format, a linear polymer (LP), as the selective recognition element for the globular protein lactoferrin (LF) is proposed as a proof-of-concept study. For the synthesis, a solid-phase strategy using the reversible deactivation radical polymerisation (RDRP) mechanism is proposed. This approach, which is usually used in molecular imprinting, involves the immobilisation of LF on the surface of a solid support, but, unlike classical imprinting, a cross-linker in the polymerisation mixture is not required. Consequently, the copolymer is soluble and flexible, thus overcoming the drawbacks associated with traditional synthetic polymers for macromolecule imprinting. This new polymer format has great potential for replacing natural antibodies in bioassays such as enzyme-linked immunosorbent assays (ELISA), dot blot, western blot, or pull-down. In our case, the linear polymer was used as a recognition element to replace natural antibodies in a LF-selective ELISA. The responses of the linear polymer between LF concentrations of 0.1 nM and 0.25 µM were studied, and a significant difference was observed between the non-specific signals and the signals measured in the presence of the polymeric material. Further, the response versus log concentration curves were fitted to a logistic equation, allowing estimation of the EC50 value: 11.8 ± 1.4 nM. We also confirmed the selective detection of LF using the competitive inhibition of the selective LF-biotin conjugate (LF-Bi) binding to the plastic receptor (LP) for closely related proteins (e.g. those having similar molecular weights or isoelectric points) such as human lysozyme, trypsin, and albumin, which are present in human body fluids. The system presents a cross-reactivity value or selectivity of 1.95% for lysozyme, 0.028% for trypsin, and 0.016% for albumin. The applicability of this method for the determination of urine LF levels in inflammatory and infectious diseases of the human urinary tract is also demonstrated.

Hydrocarbon exposure effect on energetic metabolism and immune response in Crassostrea virginica.

Crassostrea virginica was exposed to different light crude oil levels to assess the effect on transcriptomic response and metabolic rate. The exposure time was 21 days, and levels of 100 and 200 µg/L were used, including a control. The most significant difference among treatments was the overexpression of several genes associated with energy production, reactive oxygen species (ROS) regulation, immune system response, and inflammatory response. Also, a hydrocarbon concentration-related pattern was identified in ROS regulation, with a gene expression ratio near 1.8:1 between 200 and 100 µg/L treatments. Statistical analysis showed no interaction effect for metabolic rate; however, significant differences were found for oil concentration and time factors, with a higher oxygen consumption at 200 µg/L. Our findings provide novel information about the metabolic response of C. virginica during hydrocarbons exposure. In addition, our results point out which biological processes should be investigated as targets for searching bioindicators.

[Oral ketamine-midazolam premedication of uncooperative patients in major outpatient surgery]. / Premedicación con ketamina-midazolam oral en pacientes no colaboradores en cirugía mayor ambulatoria.

BACKGROUND: Currently, ketamine is not often used as an anesthetic. Its clinical characteristics and mechanism of action largely depend on antagonism of the N-methyl-D-aspartate receptor. OBJECTIVE: To evaluate the utility of oral ketamine as a preanesthetic agent to lower surgical stress for patients with mental disability. MATERIAL AND METHODS: Observational, retrospective study of 112 mentally disabled patients undergoing major dental surgery on an outpatient basis. The study group received oral midazolam, ibuprofen, and 6 mg/kg of ketamine; the control group received only midazolam and ibuprofen. We recorded data concerning demographics, anesthesia, surgery, physiologic variables, Glasgow score, time of onset of anxiolysis, duration of stay in the recovery ward, and adverse events. RESULTS: Conservative odontologic treatment was provided in 66.3% of the cases. Seventy-one patients (64.4%) were in the control group and 41 patients (36.6%) in the study group. Hemodynamic, respiratory, and neurologic changes were minimal and there were no significant between-group differences. Level of sedation differed significantly between groups (P = .001) at 15 and 30 minutes; differences were also observed within the study group. Mean (SD) duration of surgery was 72.6 (29.7) minutes. Mean duration of stay in the postoperative recovery ward was 140.9 (52.1) minutes (135.8 [54.89] minutes in the study group and 144.2 [50.5] minutes in the control group). The incidence of adverse events did not differ significantly between groups. CONCLUSIONS: Oral ketamine is an effective premedication for major ambulatory surgery and does not increase the incidence of side effects.

Recent trends in prostate cancer in Spain. / Tendencias recientes en cáncer de próstata en España.

OBJECTIVE: To assess recent trends in prostate cancer incidence, survival and mortality in Spain using updated data. SUBJECTS AND METHOD: Prostate cancer mortality data have been obtained from the National Institute of Statistics (INE). Incidence cases have been obtained from the databases Cancer Incidence in Five Continents (CI5) and European Cancer Information System. Joinpoint regression models were used for trend analysis. The results show the duration (years) of each trend, as well as the Annual Percent Change (APC) for each of them. The direction and magnitude of recent trends (last 5 years available) were evaluated using the percentages of Average Annual Percent Change (AAPC). RESULTS: Incidence rates increased significantly from 16.4 in 1980 to 61.3 in 2014. The joinpoint analysis shows three periods: two initial periods of significant rise (1980-1990; 3.5% and 1990-2004; 8.4%) followed by a final one in which rates stabilize (2004-2014; -0.5%, non-significant). Mortality rates drop from 12.9 in 1980 to 7.9 in 2018, with an AAPC of -1.2% (p<0.05). However, the joinpoint analysis identified three time periods: an initial period of statistically significant rise (1980-1998; APC: 0.6%, p<0.05) and two periods of decreasing rates (1992-2008; APC: -3.3%, p<0.05 and 2008-2018; APC: -2.4%, p<0.05). CONCLUSION: Recent trends (last 5 years) show that mortality rates have decreased and incidence rates have stabilized or even decreased in some age groups.

Learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. / Curva de aprendizaje en el manejo de los inhibidores de tirosina quinasa como primera línea de tratamiento en pacientes con cáncer renal metastásico.

OBJECTIVES: To analyse the learning curve for the management of tyrosine kinase inhibitors as the first line of treatment for patients with metastatic renal cancer. MATERIAL AND METHODS: We evaluated 32 consecutive patients treated in our department for metastatic renal cancer with tyrosine kinase inhibitors (pazopanib or sunitinib) as first-line treatment between September 2012 and November 2015. We retrospectively analysed this sample. We measured the time to the withdrawal of the first-line treatment, the time to progression and overall survival using Kaplan-Meier curves. The learning curve was analysed with the cumulative sum (CUSUM) methodology. RESULTS: In our series, the median time to the withdrawal of the first-line treatment was 11 months (95% CI 4.9-17.1). The mean time to progression was 30.4 months (95% CI 22.7-38.1), and the mean overall survival was 34.9 months (95% CI 27.8-42). By applying the CUSUM methodology, we obtained a graph for the CUSUM value of the time to withdrawal of the first-line treatment (CUSUM TW), observing 3 well-differentiated phases: phase 1 or initial learning phase (1-15), phase 2 (16-26) in which the management of the drug progressively improved and phase 3 (27-32) of maximum experience or mastery of the management of these drugs. The number of treated patients needed to achieve the proper management of these patients was estimated at 15. CONCLUSIONS: Despite the limitations of the sample size and follow-up time, we estimated (in 15 patients) the number needed to reach the necessary experience in the management of these patients with tyrosine kinase inhibitors. We observed no relationship between the time to the withdrawal of the first-line treatment for any cause and progression.

Low-dose-rate brachytherapy for prostate cancer in renal transplant recipients.

PURPOSE: Prostate cancer (PCa) is the most common malignancy among men and one of the most common neoplasms affecting renal transplant recipients (RTRs). The available treatments for localized PCa among the general population (GP), surgery and external beam radiotherapy, carry a risk of damage to the transplanted kidney, the ureters, and the bladder and therefore tend to be avoided by most groups. The objective of this study was to assess the efficacy and feasibility of low-dose-rate brachytherapy (LDR-BT) for PCa in RTRs. METHODS AND MATERIALS: We carried out a retrospective review on all RTRs diagnosed of PCa who had undergone LDR-BT at our institution between 2000 and 2015. Nine patients met these criteria, but 1 did not fulfill the followup. Hence, we analyzed 8 patients. We reviewed all clinical data for PCa and graft function in these patients and compared the results with the GP. RESULTS: Mean baseline prostate-specific antigen was 6.8 ± 1.9 ng/mL. All PCa had a Gleason score of 6 and were classified as low risk according the Europe Association of Urology guidelines. Mean followup after seed implantation was 48 ± 12.8 months. All 8 patients remain free of prostate-specific antigen failure. Five-year progression-free survival, cancer-specific survival, and overall survival rates were 100%, 100%, and 62.5%. There was no specific toxicity associated with LDR-BT, and there were no acute adverse events affecting the graft. CONCLUSIONS: LDR-BT is a feasible and acceptable treatment for localized PCa in RTRs. Oncological outcomes are similar to the GP, and there is minimal toxicity to the renal graft.

Role of protein kinase C, G-protein coupled receptors, and calcium flux during metamorphosis of the sea urchin Strongylocentrotus purpuratus.

Artificial inducers have been used to study signal-transduction pathways involved in metamorphosis of some marine invertebrates. However, the transduction mechanisms for echinoderms have been less explored. In the present study, participation of protein kinase C (PKC), G-protein-coupled receptors (GPCRs), and calcium has been investigated during metamorphosis of the sea urchin Stronglylocentrotus purpuratus. Competent larvae were induced with different drugs that activate (PKC and GP activators, Ca2+ ionophores, and inhibitors of Ca2+ ATPase) or inhibit (PKC, G-protein, and Ca2+ flux inhibitors) metamorphosis. Six of the compounds were effective: the PKC activators TPA and indolactam; the G-protein inhibitors suramin and guanosine; the calcium ionophore A23187, and the calcium ATPase inhibitor thapsigargin. TPA was effective at 0.001 microM; indolactam was effective at 0.001 microM. In the presence of KCl as inducer, the G-protein inhibitor suramin was effective at 10 microM and guanosine at 0.001 microM. In the presence of a bacterial film as inducer, suramin was effective at 50 microM, and guanosine inhibited metamorphosis at 1 microM. A23187 was effective at 5 and 10 microM and thapsigargin at 50 and 100 microM. Our results indicate that GPCRs, protein kinase C, and calcium participate in the metamorphosis of S. purpuratus. These elements of the transduction pathways triggered during metamorphosis may be part of a cascade of signal transduction routes that interact from induction to the end of the morphogenetic events that shape the postlarval form. In addition, according to the results obtained with G-protein inhibitors, the GPCRs may be shared between the artificial (KCl) and natural (biofilm) inducers.

Boron neutron capture therapy for murine malignant gliomas.

Boron neutron capture therapy (BNCT) involves administration of a boron compound followed by neutron irradiation of the target organ. The boron atom captures a neutron, which results in the release of densely ionizing helium and lithium ions that are highly damaging and usually lethal to cells within their combined track length of approximately 12 microns. Prior to Phase I clinical trials for patients with malignant gliomas, mice with glioma 261 intracerebral tumors were fed D,L-3-(p-boronophenyl)alanine and irradiated with total tumor doses of 1000-5000 RBE-cGy of single fraction thermal neutrons to determine the maximum tolerated dose and effect on survival. These mice were compared to mice that received D,L-3-(p-boronophenyl)alanine alone, neutron irradiation alone, photon irradiation alone, or no treatment. Additional normal mice received escalating doses of neutron irradiation to determine its toxicity to normal brain. BNCT caused a dose-dependent, statistically significant prolongation in survival at 1000-5000 RBE-cGy. At 3000 RBE-cGy, median survival rates of the BNCT and untreated control groups were 68 and 22 days, respectively, with a long-term survival rate of 33%. At 4000 RBE-cGy, median survival was 72 and 21 days, respectively, with a long-term survival rate of 43%. At lower radiation doses, the extended survival was comparable between the BNCT and photon-irradiated mice; however, at 3000 and 4000 RBE-cGy the median survival of BNCT-treated mice was significantly greater than photon-irradiated mice. The maximum tolerated single fraction dose to normal brain was approximately 2000 RBE-cGy.

Comparison of pathological data between prostate biopsy and radical prostatectomy specimen in patients with low to very low risk prostate cancer.

OBJECTIVE: To analyze the correlation between pathological data found in radical prostatectomy and previously performed biopsy in patients at low risk prostate cancer. MATERIAL AND METHODS: A descriptive, cross-sectional study was conducted to assess the characteristics of radical prostatectomies performed in our center from January 2012 to November 2014. The inclusion criteria were patients with low-risk disease (cT1c-T2a, PSA≤10ng/mL and Gleason score≤6). We excluded patients who had fewer than 8 cores in the biopsy, an unspecified number of affected cores, rectal examinations not reported in the medical history or biopsies performed in another center. RESULTS: Of the 184 patients who underwent prostatectomy during this period, 87 met the inclusion criteria, and 26 of these had<3 affected cores and PSA density≤.15 (very low risk). In the entire sample, the percentage of undergrading (Gleason score≥7) and extracapsular invasion (pT3) was 18.4% (95% CI 10.3-27.6) and 10.35% (95% CI 4.6-17.2), respectively. The percentage of positive margins was 21.8% (95% CI 12.6-29.9). In the very low-risk group, we found no cases of extracapsular invasion and only 1 case of undergrading (Gleason 7 [3+4]), representing 3.8% of the total (95% CI 0-12.5). Predictors of no correlation (stage≥pT3a or undergrading) were the initial risk group, volume, PSA density and affected cores. CONCLUSIONS: Prostate volume, PSA density, the number of affected cores and the patient's initial risk group influence the poor pathological prognosis in the radical prostatectomy specimen (extracapsular invasion and Gleason score≥7).

Has prostate cancer mortality stopped its decline in Spain?

OBJECTIVE: To describe the evolution of prostate cancer mortality in Spain during the period 1980-2013. SUBJECT AND METHOD: The prostate cancer mortality data and population data needed to calculate the indicators were provided by the National Institute of Statistics. We calculated the specific rates by age group, raw and standardised globally using the direct method (European standard population). The rates are expressed for 100,000 person-years. For the analysis of trends in the rates, we used joinpoint regression models. RESULTS: The overall rates adjusted for age in Spain decreased from 21.7 to 15.4 deaths per 100,000 men-years between the starting and ending date of the study period (annual percentage change: -.9%; P<.05). The joinpoint analysis reflects 2 periods: 1980-1998 (.7% annual increase; P<.05) and 1998-2013, during which the rates decreased significantly (-3%; P<.05). Except for the autonomous cities of Ceuta and Melilla where the rates remained stable over the course of the study period, the communities showed 1 or 2 points of inflection in the trends, and all had a final period with a reduction in the rates (except for Galicia and Catalonia, where the rates stabilised in 2008-2013). CONCLUSION: The decline in prostate cancer mortality in Spain appears to have stopped in Galicia and Catalonia.

Morphology and topographical organization of the retrospleniocollicular connection: a pathway to relay contextual information from the environment to the superior colliculus.

The retrospleniocollicular connection is of interest because it constitutes one link between the limbic system, which is considered the anatomical substrate of emotional experience, and the superior colliculus (SC), which mediates approach and avoidance behavior. The morphology, topography, and origin of the retrospleniocollicular connections were studied by using anterograde [biotinylated dextranamine 10,000 (BDA)] and retrograde [Fluoro-Gold (FG)] tracers. After BDA injections involving retrosplenial granular and agranular cortices, terminal fibers innervating all collicular layers except stratum griseum superficiale were found throughout nearly the entire colliculi. Axons branched within restricted portions of the dorsoventral collicular axis with variable morphologies, suggesting functional heterogeneity. Terminal fields originating in anterior and posterior regions of the retrosplenial cortex were preferentially distributed in laterodorsal and medioventral collicular regions, respectively, but there were also large, densely innervated regions in which the terminal fields overlapped. FG injections in the SC confirmed the retrospleniocollicular topography and demonstrated that this connection originated from layer V pyramidal cells of all retrosplenial areas. The distribution of retrospleniocollicular boutons was related to that of the AChE modules, which are associated with connections in the intermediate layers of the SC. In lateral portions of the SC intermediate layers, most retrospleniocollicular boutons were found in medium AChE stained regions, whereas in medial portions, they terminated in AChE-poor domains. The present results demonstrate that the retrosplenial cortex is the origin of a broad and dense network of axonal branches that may modulate SC-mediated motor and physiological responses involved in emotional behavior.

Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing.

Splenic immune function is modulated by sympathetic innervation, which in turn is controlled by inputs from supraspinal regions. In the present study, the characterization of central circuits involved in the control of splenic function was accomplished by injecting pseudorabies virus (PRV), a retrograde transynaptic tracer, into the spleen and conducting a temporal analysis of the progression of the infection from 60 hours to 110 hours postinoculation. In addition, central noradrenergic cell groups involved in splenic innervation were characterized by dual immunohistochemical detection of dopamine-beta-hydroxylase and PRV. Infection in the CNS first appeared in the spinal cord. Splenic sympathetic preganglionic neurons, identified in rats injected with Fluoro-Gold i.p. prior to PRV inoculation of the spleen, were located in T(3)-T(12) bilaterally; numerous infected interneurons were also found in the thoracic spinal cord (T(1)-T(13)). Infected neurons in the brain were first observed in the A5 region, ventromedial medulla, rostral ventrolateral medulla, paraventricular hypothalamic nucleus, Barrington's nucleus, and caudal raphe. At intermediate survival times, the number of infected cells increased in previously infected areas, and infected neurons also appeared in lateral hypothalamus, A7 region, locus coeruleus, subcoeruleus region, nucleus of the solitary tract, and C3 cell group. At longer postinoculation intervals, infected neurons were found in additional hypothalamic areas, Edinger-Westphal nucleus, periaqueductal gray, pedunculopontine tegmental nucleus, caudal ventrolateral medulla, and area postrema. These results demonstrate that the sympathetic outflow to the spleen is controlled by a complex multisynaptic pathway that involves several brainstem and forebrain nuclei.

Role of locus coeruleus in foot shock-evoked Fos expression in rat brain.

The robust activation of locus coeruleus neurons in response to a variety of stressors, in conjunction with the widespread outputs of the locus coeruleus, suggest that the locus coeruleus may be important in mediating responses to stress. Previous studies in rats have demonstrated that exposure to foot shock elicits Fos expression, a marker of neuronal activation, in the locus coeruleus and other brain sites. In order to evaluate the involvement of the locus coeruleus in foot shock-induced activation of other brain sites, shock-induced Fos expression was examined in the locus coeruleus and other brain areas known to be activated by foot shock, following direct inhibition of the locus coeruleus by local infusion of muscimol, a GABA agonist, prior to foot shock. Control rats received infusions of artificial cerebrospinal fluid into the locus coeruleus or muscimol into areas outside of locus coeruleus. Rats infused with artificial cerebrospinal fluid and then exposed to foot shock had significant increases in Fos expression in several brain areas, including locus coeruleus, nucleus O, several subdivisions of the hypothalamus, subnuclei of amygdala, bed nucleus of the stria terminalis and cingulate cortex. Inhibition of the locus coeruleus prior to foot shock significantly inhibited Fos expression in the locus coeruleus, nucleus O, some subdivisions of the hypothalamus including the magnocellular and medial parvicellular paraventricular hypothalamic nucleus, subnuclei of amygdala, and cingulate cortex. In contrast, inhibition of the locus coeruleus did not affect shock-induced Fos expression in other areas, including certain subdivisions of the hypothalamus and bed nucleus of the stria terminalis. We suggest that foot shock may activate multiple pathways, with activation of certain discrete nuclei requiring input from the locus coeruleus and activation of others occurring independently of locus coeruleus input.

Opposite modulation of capsaicin-evoked substance P release by glutamate receptors.

Substance P and glutamate are present in primary afferent C-fibers and play important roles in persistent inflammatory and neuropathic pain. In the present study, we have examined whether activation of different glutamate receptor subtypes modulates the release of substance P evoked by the C-fiber selective stimulant capsaicin (1 microM) from rat trigeminal nucleus slices. The selective NMDA glutamate receptor agonist L-CCG-IV (1-10 microM) enhanced capsaicin-evoked substance P release about 100%. This facilitatory effect was blocked by 0.3 microM MK-801, a selective NMDA receptor antagonist. The metabotropic glutamate receptor agonists L-AP4 (group III) and DHPG (group I) (30-100 microM) inhibited capsaicin-evoked substance P release by approximately 60%. These inhibitory effects were blocked by the selective metabotropic glutamate receptor antagonist (+/-)-MCPG (5 microM). On the other hand, AMPA and kainate (0.1-10 microM), did not significantly affect capsaicin-evoked substance P release. Thus, substance P release from non-myelinated primary afferents, and possibly nociception, may be under the functional antagonistic control of some metabotropic and ionotropic glutamate receptor subtypes.

Cryptosporidiosis among patients with acquired immunodeficiency syndrome in Zulia State, Venezuela.

We studied the prevalence of Cryptosporidium in 29 patients with acquired immunodeficiency syndrome (AIDS) from Zulia State, Venezuela. They ranged in age from five months to 46 years. Two were children and 27 were adults, of which six were women. Of the 21 men, 66.6% reported homosexual behavior. Three stool samples from each patient were examined, and modified Ziehl-Neelsen carbolfuchsin staining of formalinether stool concentrates was used to identify Cryptosporidium oocysts. To detect the presence of other intestinal parasites, direct wet mounts and iron-hematoxylin-stained smears were examined. Cryptosporidium was found in 12 (41.3%) of the patients and was identified as a single parasitic infection in seven of the 12 patients (58.3%). Other pathogenic parasites encountered were Giardia lamblia (3 of 12, 25%), Entamoeba histolytica (1 of 12, 8.3%), Ascaris lumbricoides, Trichuris trichiura, and Strongyloides stercoralis (each 1 of 12, 8.3%). Blastocystis hominis, an organism with an uncertain taxonomic position and pathogenicity, was observed in three of 12 patients (25%). An inflammatory exudate was observed in 10 of 12 patients infected with Cryptosporidium. Most of the patients with this infection presented with chronic watery diarrhea and weight loss. Our results suggest that Cryptosporidium is very common in AIDS patients with diarrhea in Venezuela. However, the role of this parasite as an enteropathogen in these patients is uncertain.

Cryptosporidium infections in a suburban community in Maracaibo, Venezuela.

A point prevalence survey for Cryptosporidium was conducted in 212 subjects two months to 70 years of age in a suburban area with a low socioeconomic status in Maracaibo City, Venezuela. Single stool specimens were collected and modified Ziehl-Neelsen carbol-fuchsin staining of 10% formalin-preserved stool was used to identify Cryptosporidium oocysts. Direct wet mounts, iron-hematoxylin-stained smears and formalin-ether concentrates were examined to determine the presence of other intestinal parasites. Cryptosporidium infections were identified in 21 subjects (9.9%), with a high percentage of asymptomatic carriers (15 of 21, 71.4%). Six children (28.5%) had gastrointestinal symptoms and four of them were infants. Cryptosporidium was the single detectable potential pathogenic parasite in only five (23.8%) of 21 patients. The infection rate with one or more parasites was high (82%) and multiple infections, including pathogenic helminths and protozoa, were observed in the majority of patients who passed oocysts. Our findings suggest that although Cryptosporidium is an important pathogen, the proportion of asymptomatic carriers may be high in areas of low socioeconomic status in developing countries.

Changes of the cholinergic input to the superior colliculus following enucleation in neonatal and adult rats.

The effects of neonatal and adult enucleation on the adult pattern of cholinergic inputs to the rat superior colliculus (SC) was analysed. In the superficial layers immunohistochemical labelling revealed that choline acetyltransferase (ChAT) was predominantly confined to single boutons which were almost continuously distributed throughout the rostrocaudal and lateromedial axes. In these layers a higher density of boutons was observed in the stratum zonale (SZ) and lower stratum griseum superficiale (SGSl) than in the upper stratum griseum superficiale (SGS(u)) and stratum opticum (SO). In intermediate collicular layers ChAT-immunostaining was mainly found in axonal profiles which were arranged in a patchy fashion. Neonatal enucleation caused a drastic increase in bouton density in the SZ, SGS(u) and SGSl. The density of boutons was particularly high in the SGS(u), giving the appearance of an almost homogeneous distribution of boutons from the collicular surface down to the upper limit of SO. Visual deafferentiation at the adult stage was followed by an increase in the bouton density exclusively in the SZ. Neonatal enucleation produced a dorsoventral enlargement of the region containing patches of ChAT staining which was slightly greater following adult deafferentiation. The results described here show that after visual deafferentiation an increase in ChAT innervation to superficial and intermediate collicular layers occurs, providing new information regarding plasticity in the visual system. In view of previous data on cholinergic function in the central nervous system, such an increase could compensate for the loss of retinal excitatory input by facilitating neuronal responses in the SC.

Dynorphin A increases substance P release from trigeminal primary afferent C-fibers.

Dynorphin A-(1-17) has been found to produce spinal antianalgesia and allodynia. Thus, we studied whether dynorphin A-(1-17) modulates substance P release evoked by the C-fiber-selective stimulant capsaicin (1 microM) from trigeminal nucleus caudalis slices. Very low concentrations of dynorphin A-(1-17) (0.01-0.1 nM) strongly facilitated capsaicin-evoked substance P release. This dynorphin A-(1-17) effect was not blocked by the opioid receptor antagonists naloxone (100 nM), beta-funaltrexamine (20 nM), naloxonazine (1 nM), nor-binaltorphimine (3 nM) and ICI 174,864 (N,N-dialyl-Tyr-Aib-Phe-Leu; 0.3 microM). Yet, the effect of dynorphin A-(1-17) was blocked by the NMDA receptor antagonist MK-801 ((+)-5-methyl-10,11-dihydro-5H-dibenzo[a,d] cyclohepten-5-10-imine maleate; 0.3 microM). Neonatal treatment with capsaicin (50 mg/kg s.c.), which destroys substance P-containing primary afferents, abolished the excitatory effect of dynorphin A-(1-17) on K+-evoked substance P release. In conclusion, dynorphin A-(1-17) increases substance P release from C-fibers by the activation of NMDA receptors which supports the involvement of presynaptic mechanisms in dynorphin-induced antianalgesia and allodynia.