NAT2 global landscape: Genetic diversity and acetylation statuses from a systematic review.

Arylamine N-acetyltransferase 2 has been related to drug side effects and cancer susceptibility; its protein structure and acetylation capacity results from the polymorphism's arrays on the NAT2 gene. Absorption, distribution, metabolism, and excretion, cornerstones of the pharmacological effects, have shown diversity patterns across populations, ethnic groups, and even interethnic variation. Although the 1000 Genomes Project database has portrayed the global diversity of the NAT2 polymorphisms, several populations and ethnicities remain underrepresented, limiting the comprehensive picture of its variation. The NAT2 clinical entails require a detailed landscape of its striking diversity. This systematic review spans the genetic and acetylation patterns from 164 articles from October 1992 to October 2020. Descriptive studies and controls from observational studies expanded the NAT2 diversity landscape. Our study included 243 different populations and 101 ethnic minorities, and, for the first time, we presented the global patterns in the Middle Eastern populations. Europeans, including its derived populations, and East Asians have been the most studied genetic backgrounds. Contrary to the popular perception, Africans, Latinos and Native Americans have been significantly represented in recent years. NAT2*4, *5B, and *6A were the most frequent haplotypes globally. Nonetheless, the distribution of *5B and *7B were less and more frequent in Asians, respectively. Regarding the acetylator status, East Asians and Native Americans harboured the highest frequencies of the fast phenotype, followed by South Europeans. Central Asia, the Middle East, and West European populations were the major carriers of the slow acetylator status. The detailed panorama presented herein, expands the knowledge about the diversity patterns to genetic and acetylation levels. These data could help clarify the controversial findings between acetylator states and the susceptibility to diseases and reinforce the utility of NAT2 in precision medicine.

Urinary androgens excretion patterns and prostate cancer in Mexican men.

Epidemiological studies related to androgens and prostate cancer (PC) have focused on serum determination of testosterone, androstenedione (A4), and DHEA, with inconsistent results. Herein, we hypothesized that differences in androgen biosynthetic and metabolic pathways, rather than differences in specific androgen concentrations, are associated with prostatic carcinogenesis. Therefore, spot urine samples from 111 incident PC cases with Gleason score at diagnosis and 227 healthy population controls, were analyzed. Urinary androgen concentrations (nanograms/milligrams of creatinine) were determined by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS). Using a factor analysis, we identified three androgen urinary excretion patterns. In a subsample, we evaluated a modification effect of the androgen receptor (AR) CAG polymorphism. Pattern I, characterized by A4 and testosterone hydroxylated metabolites (11ß-OHT; 2ß-OHT; 15ß-OHT; 2α-OHT; 6ß-OHT), was associated with high PC odds among carriers of AR gene (CAG)>19 repeats (OR: 3.67 95% CI: 1.23-11.0; P for interaction= 0.009). Conversely, higher testosterone excretion (pattern III), was marginally associated with lower (OR: 0.35 95% CI: 0.12-1.00, P for trend= 0.08) poorly differentiated PC (Gleason ≥8). No clear association was observed with pattern II (DHEA; 16α and 16ß-OHT). Our results were consistent with the previous evidence which suggests that the C11-oxy backdoor pathway is important for prostatic carcinogenesis. Androgen urine excretion analysis could be useful for PC diagnosis, treatment, and prognosis; however, further studies with a larger number of samples and the urinary determination of 11-ketoandrogens are necessary.

Temephos Decreases Sperm Quality and Fertilization Rate and Is Metabolized in Rat Reproductive Tissues at Low-Dose Exposure.

Temephos is an organophosphorus pesticide used in control campaigns against vectors that transmit diseases, including dengue, a public health concern. The WHO classifies temephos in category III and its safe concentration (low-observable-adverse-effect level) in male rats is 100 mg/kg/day for up to 44 days. Temephos inhibits acetylcholinesterase (AChE) and is metabolized in different tissues, probably by mixed-function oxidases; one of its metabolites is bisphenol S (BPS), which is considered an endocrine disruptor. The aim of this study was to evaluate the effects of temephos on sperm function and its biotransformation in the testis, epididymis, and other tissues to explore its toxicity in rats treated with 100 mg/kg/day/5 or 7 days (gavage). AChE activity was inhibited 70% starting on day 3 and 13 or 41% mortality was observed at 5 or 7 days, respectively. After 7 days, temephos significantly decreased sperm motility (30%) and viability (10%) and increased (10%) lipoperoxidation, and the sperm DNA exhibited no damage. Temephos was distributed and metabolized in all tissues, with the highest levels observed in the adipose tissue and temephos levels were 16-fold higher in the epididymis than in the testis. Notably, BPS was observed in the testis. At 5 days, decreased sperm motility (12.5%) and viability (5.7%) were observed and sperm fertilization decreased (30%). These results suggest that temephos decreases sperm quality and fertilization capacity at recommended safe concentrations and that it is metabolized in male reproductive tissues. This pesticide places the reproductive health of exposed people at risk, suggesting the need to reevaluate its toxicity.

Toxicokinetics of temephos after oral administration to adult male rats.

Temephos (Tem) is the larvicide of choice to control mosquito transmission of dengue, Zika, and chikungunya. The toxicokinetic and toxicological information of temephos is very limited. The aim of this work was to determine the toxicokinetics and dosimetry of temephos and its metabolites. Male Wistar rats were orally administered temephos (300 mg/kg) emulsified with saline solution and sacrificed over time after dosing. Temephos and its metabolites were analyzed in blood and tissues by high performance liquid chromatography-diode array detector. At least eleven metabolites were detected, including temephos-sulfoxide (Tem-SO), temephos-oxon (Tem-oxon), temephos-oxon-sulfoxide (Tem-oxon-SO), temephos-oxon-SO-monohydrolyzed (Tem-oxon-SO-OH), 4,4´-thiodiphenol, 4,4´-sulfinyldiphenol, and 4,4´-sulfonyldiphenol or bisphenol S (BPS). The mean blood concentrations of temephos were fitted to a one-compartment model for kinetic analysis. At 2 h, the peak was reached (t1/2 abs = 0.38 h), and only trace levels were detected at 36 h (t1/2 elim = 8.6 h). Temephos was detected in all tissues and preferentially accumulated in fat. Temephos-sulfone-monohydrolyzed (Tem-SO2-OH) blood levels remained constant until 36 h and gradually accumulated in the kidney. Tem-oxon was detected in the brain, liver, kidney, and fat. Clearance from the liver and kidney were 7.59 and 5.52 ml/min, respectively. These results indicate that temephos is well absorbed, extensively metabolized, widely distributed and preferentially stored in adipose tissue. It is biotransformed into reactive metabolites such as Tem-oxons, Tem-dioxons, and BPS. Tem-SO2-OH, the most abundant metabolite of temephos, could be used as an exposure biomarker for toxicokinetic modeling. These results could provide critical insight into the dosimetry and toxicity of temephos and its metabolites.

Analysis of testosterone-hydroxylated metabolites in human urine by ultra high performance liquid chromatography-Mass Spectrometry.

Testosterone regulates the male reproductive system and acts directly or indirectly on nearly all systems during fetal, pubertal and adult life. Testosterone homeostasis depends on its synthesis and degradation. The major biotransformation reactions are hydroxylation by different cytochrome P450 (CYP) isoforms. There are no described methods to determine the profile of testosterone-hydroxylated metabolites in human urine. The aim of this study was to develop an analytical method to determine testosterone-hydroxylated metabolites in human urine using UPLC-MS. Seven testosterone-hydroxylated metabolites, androstenedione, and testosterone, were identified by comparison of their tret and positive electrospray ionization (ESI+) data, with those of analytical standards. The method developed is sensitive, specific, repeatable, and precise. Limits of detection and quantitation for all compounds ranged from 1.360 to 13.054 ng/ml and 4.234-39.679 ng/ml, respectively. The percentages of recovery were between 81.2 and 128.8%. The applicability of the analytical method was confirmed by analysis of urine samples obtained from two groups of healthy men (25-30 and 50-75 years old). All analytes were identified with slightly different metabolites profiles in both groups. In conclusion, the UPLC-MS method developed here was validated for the analysis of testosterone-hydroxylated metabolites in human urine.

In vitro inhibition of human red blood cell acetylcholinesterase (AChE) by temephos-oxidized products.

Temephos (Tem) is an organophosphorus pesticide widely used to kill and prevent the growth of the main vectors for the transmission of dengue, zika, and chikungunya viruses. In chlorinated water, Tem is oxidized to its dioxon-sulfoxide (Tem-dox-SO), dioxon-sulfone (Tem-dox-SO2), and sulfoxide (Tem-SO) derivatives; however, these compounds are not commercially available to be used as standards and in toxicological studies. In the present study, we synthesized and characterized the Tem-oxidation products and the compound 4,4'-sulfinyldiphenol. These compounds were obtained by a simple reaction between Tem or 4,4'-thiodiphenol with sodium hypochlorite or potassium periodate, and were characterized by IR, NMR, and UPLC-HRESIMS. The in vitro evaluation of inhibitory potency of Tem-oxidized products on human red blood cell acetylcholinesterase (RBC AChE) showed that Tem-dox-SO2 was the most potent inhibitor of human RBC AChE, and its effect was more pronounced than that observed for ethyl-paraoxon, a potent typical inhibitor of AChE. An HPLC-DAD method for the analysis of metabolic products of Tem was developed, which may be useful for monitoring in biological and environmental samples. The ability of Tem-oxidized metabolites to inhibit human RBC AChE suggests that the addition of Tem to chlorinated drinking water could result in an increase in the risk of RBC AChE inhibition after exposure.

Chronic administration of diethylnitrosamine to induce hepatocarcinogenesis and to evaluate its synergistic effect with other hepatotoxins in mice.

Hepatocellular carcinoma (HCC) arises after a long period of exposition to etiological factors that might be either independent or collectively contributing. Several rodent models resemble human HCC; however, the major limitation of these models is the lack of chronic injury that reproducibly mimics the molecular alterations as it occurs in humans. Thus, we hypothesized that chronic administration of different DEN treatments identifies the best-fit dose to induce the HCC and/or to determine whether small DEN doses act synergistically with other known hepatotoxins to induce HCC in mice. C57BL/6 J male mice were intraperitoneally injected twice a week for 6 weeks with different DEN doses ranging from 2.5 to 40 mg/kg body weight; then, selected doses (2.5, 5 and 20 mg/kg) for 6, 10, 14, and 18 weeks. We demonstrated that DEN at 20 mg/kg promoted reactive oxygen species and 4-hydroxynonenal production, cell proliferation inflammatory infiltrate, and fibrosis, which in turn induced liver cancer by week 18. These parameters were established by evaluating histopathological changes, HCC markers such as glutathione S-transferase placental-1 (Gstp1), Cytokeratin-19 (Ck19) and prostaglandin reductase-1 (Ptgr1); that of Cyp2e1, a DEN metabolizing enzyme; and the expression of the proliferation marker Ki67. While DEN at 2.5 and 5 mg/kg increased Gstp1 and Ck19, DEN at 20 mg/kg decreased them and Cyp2e1 expression and activity. In summary, our results demonstrate that DEN chronically administrated at 20 mg/kg induces the HCC, while DEN at 2.5 and 5 mg/kg could be useful in elucidating its synergistic effect with other hepatotoxic agents in mice.

In vitro phase I metabolism of vinclozolin by human liver microsomes.

1. Vinclozolin (Vin) is a fungicide used in agricultural settings and is classified as an endocrine disruptor. Vin is non-enzymatically hydrolyzed to 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2) metabolites. There is no information about Vin biotransformation in humans, therefore, the aim of this study was to characterize its in vitro metabolism using human liver microsomes. 2. Vin was metabolized to the [3-(3,5-dichlorophenyl)-5-methyl-5-(1,2-dihydroxyethyl)-1,3-oxazolidine-2,4-dione] (M4) and N-(2,3,4-trihydroxy-2-methyl-1-oxo)-3,5-dichlorophenyl-1-carbamic acid (M7) metabolites, which are unstable and gradually converted to 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutyranilide (DTMBA, formerly denoted as M5). M4 and DTMBA metabolites co-eluted in the same HPLC peak; this co-elute peak exhibited a Michaelis-Menten kinetic, whereas M7 showed a substrate inhibition kinetics. The KM app for co-eluted M4/DTMBA and M7 was 24.2 ± 5.6 and 116.0 ± 52.6 µM, the VMax app was 0.280 ± 0.015 and 0.180 ± 0.060 nmoles/min/mg protein, and the CLint app was 11.5 and 1.5 mL/min/g protein, respectively. The Ki for M7 was 133.2 ± 63.9 µM. Cytochrome P450 (CYP) chemical inhibitors furafylline (CYP1A2), ketoconazole (CYP3A4), pilocarpine (CYP2A6) and sulfaphenazole (CYP2C9) inhibited M4/DTMBA and M7 formation, suggesting that Vin is metabolized in humans by CYP. 3. DTMBA is a stable metabolite and specific of Vin, therefore, it could be used as a biomarker of Vin exposure in humans to perform epidemiological studies.

Analysis of 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (DTMBA) as a new potential biomarker of exposure to vinclozolin in urine.

Vinclozolin (V) is a fungicide with anti-androgenic properties whose metabolism is not fully understood, and data on urinary elimination of either V or its metabolites are limited. Therefore the kinetics of urinary elimination of V and its metabolites, after an oral dose in adult male rats were investigated. A single oral dose of V (100 mg/kg) suspended in corn oil was administered to male adult Wistar rats, and urine was collected at different times after dosing. V and its metabolites were extracted from urine, then enzymatically hydrolyzed using ß-glucuronidase/sulfatase of H. pomatia, and analyzed by HPLC/DAD. Urinary pharmacokinetic parameters were calculated using the analyte concentrations adjusted by creatinine levels. V and its metabolites 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (DTMBA, formerly denoted as M5), 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1), 3,5-dichloroaniline (M3), and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2) were efficiently detected. The mean urine concentrations of V and M1 metabolite were fitted to a two-compartmental model for pharmacokinetic analysis. DTMBA approximately represented 88% of the total excreted metabolites, it was easily detected up to 168 h after dosing and its half-lives were 21.5 and 74.1 h, respectively. M1 was the second most abundant metabolite and was detected up to 144 h after being void. V and M3 were detected before 48 h, and M2 exhibited the lowest levels during the first 8 h after dosing. DTMBA, the most abundant V metabolite is quickly eliminated by urine, it is chemically stable, specific and could represent a useful alternative to be used as a biomarker of exposure to V.

Vinclozolin modulates hepatic cytochrome P450 isoforms during pregnancy.

Vinclozolin (V) is classified as a potent endocrine disruptor. The aim of the present study was to determine the effects of V on rat liver CYP regulation and on serum levels of testosterone and estradiol during pregnancy. Pregnancy decreased the liver total CYP content by 65%, enzyme activities of MROD, PROD, and PNPH, and testosterone hydroxylation activities, as well as the protein content of CYP2A and 3A. V exposure remarkably induced the protein content and enzyme activities of CYP1A, 2A, 2B and 3A subfamilies. Testosterone and estradiol were affected in an opposite manner, provoking a 3.5-fold increase in the estradiol/testosterone ratio. These results suggest that V could regulate the hepatic CYP expression through interaction with receptors and coactivators involved in its expression and may play an important role in hormonal balance during pregnancy. In addition, the results may also contribute to understanding the toxicity of V by in utero exposure.

In vitro metabolism of the anti-androgenic fungicide vinclozolin by rat liver microsomes.

Vinclozolin (V) is a fungicide used in agricultural settings. V administered to rats is hydrolyzed to 2-[[(3,5-dichlorophenyl)-carbamoyl]oxy]-2-methyl-3-butenoic acid (M1) and 3',5'-dichloro-2-hydroxy-2-methylbut-3-enanilide (M2). V, M1 and M2 have antiandrogenic properties by interacting with the androgen receptor. Data on V, M1 and M2 biotransformation are limited. Our objective was to characterize V metabolism by rat liver microsomes. V was incubated with non-treated adult male Long-Evans rat liver microsomes and NADPH. Several metabolites were detected following the extraction of incubate with acetonitrile and analysis by HPLC/DAD/MSD. One metabolite was identified as [3-(3,5-dichlorophenyl)-5-methyl-5-(1,2-dihydroxyethyl)-1,3-oxazolidine-2,4-dione] (M4), which was gradually converted to 3',5'-dichloro-2,3,4-trihydroxy-2-methylbutylanilide (M5). Both co-eluted in the same HPLC peak. Another metabolite ([M7]) was detected by UV but was unstable for mass spectral analysis. The K(M app) for co-eluted M4/M5 and [M7] was 53.7 and 135.4 µM, the V(max app) was 0.812 and 0.669 nmoles/min/mg protein, and CL(int) was 15.1 and 4.9 ml/min/g protein, respectively. Pilocarpine, orphenadrine and proadifen and anti-rat cytochrome P450 (CYP)2A, 2B and 3A antibodies inhibited M4/M5 and [M7] formation. These results indicate that V is efficiently metabolized by CYP. Determination of the metabolites of V will provide further insight into the relationship between toxicity and tissue dose of V and its metabolites.

Condritis auricular. Modelo experimental en rata / Auricular chondritis. Experimental model in rat

El modelo general de inflamación local en rata se desarrolla en la almohadilla plantar. En otorrinolaringología puede haber un modelo de inflamación local en la oreja de rata mediante la producción de una condritis auricular. Para ello hemos protocolizado la metodología. La inducción de la inflamación se realiza mediante la sustancia vegetal carrageenan. Se ha comprobado mediante estudio histológico la inflamación producida, así como se ha estudiado la acción de compuestos antiinflamatorios, proinflamatorios e inflamatorios.La inflamación se ha medido con nonius y con determinación de la actividad de la enzima mieloperoxidasa. Tras los estudios realizados podemos validar la condritis auricular en rata como un modelo experimental de inflamación local en otorrinolaringología (AU)

The general pattern of local inflammation in the rat is developed in the pad of the paw. In otorhinolaryngology a model of local inflammation can be reached in the rat ear by means of the production of an auricular chondritis. For that, we have protocolized the methodology. The induction of inflammation is carried out by the substance vegetable carrageenan. It has been verified by histological studies the inflammation generated, as well as studying the action of antiinflammatory, proinflammatory and inflammatory compounds. The inflammation has been measured by nonius and by determination of the activity of the myeloperoxidase enzyme. After these studies we can validate the auricular chondritis in rat as an experimental model of local inflammation in otorhinolaryngology (AU)

Terapia sonora secuencial en acúfenos / Sequential sound therapy in tinnitus

La terapia sonora secuencial es un tratamiento de los acúfenos con ruido blanco que tiene unas características propias. Se describen la metodología, así como sus diferencias y similitudes con la Tinnitus Retraining Therapy. La terapia sonora secuencial se ha realizado a diecisiete pacientes atendidos durante el año 2002. Se adaptaron 26 generadores de sonidos, de ellos, 22 generadores de sonidos con audífono incorporado. Se compararon los resultados de la terapia sonora secuencial con los resultados del tratamiento con sonidos de la Tinnitus Retraining Therapy efectuada a 15 pacientes atendidos durante los años 2000 y 2001. El porcentaje de resultados satisfactorios obtenidos con la terapia sonora secuencial ha sido del 100 por ciento, mientras que la terapia con sonidos de la Tinnitus Retraining Therapy obtuvo un 33 por ciento. Con la terapia sonora secuencial a 6 pacientes les han desaparecido los acúfenos. Con la terapia sonora secuencial ningún paciente ha abandonado el tratamiento. Con el tratamiento con sonidos de la Tinnitus Retraining Therapy abandonaron la terapia el 53 por ciento (AU)

The sequential sound therapy is a treatment for tinnitus with white noise that has some own characteristics. We describe the methodology, as well as their differences and similarities with the Tinnitus Retraining Therapy. The sequential sound therapy has been carried out to seventeen patients assisted during the year 2002. 26 generators of sound were adapted, of them, 22 had incorporated an earphone. The results of the sequential sound therapy were compared with those of the Tinnitus Retraining Therapy in 15 patients assisted during 2000 and 2001. The percentage of satisfactory results obtained with sequential sound therapy has been a 100%, while the therapy with sounds of the Tinnitus Retraining Therapy obtained a 33%. With the sequential sound therapy 6 patients had no further tinnitus. With the sequential sound therapy no patients has abandoned the treatment. With the treatment with sounds of the Tinnitus Retraining Therapy of the patients did give up the therapy 53% (AU)

Sulpirida como tratamiento de inicio en la terapia de rehabilitación del acúfeno / Sulpiride as initial treatment in tinnitus retraining therapy

Pretendemos con este estudio conocer la interacción de un medicamento como la sulpirida en la patología del acúfeno. Esto nos ayudaría a controlar mejor su terapia de rehabilitación. Material y métodos: Los pacientes con acúfenos fueron 100, divididos en dos grupos de 50 de forma aleatoria según su llegada a la consulta. Se les administró 50 mg de sulpirida o placebo cada 8 horas durante tres meses, con controles mensuales. Se registraron la respuesta clínica, la audiometría tonal, timpanometría y acufenometría. Resultados: Durante el primer mes de tratamiento se obtuvo un 58 por ciento de mejoría en los pacientes tratados con sulpirida y un 17 por ciento en los pacientes con placebo, con significación estadística. Durante el segundo mes de tratamiento se obtuvo el 41 por ciento y 20 por ciento respectivamente. Y durante el tercer mes los resultados fueron del 42 por ciento y 17 por ciento, respectivamente. Conclusión: En pacientes con acúfenos de larga evolución el tratamiento medicamentoso con sulpirida ha conseguido mejorar a más de la mitad de los casos durante el primer mes de terapia. Tiempo crucial para que el comienzo de la terapia de rehabilitación del acúfeno resulte más efectivo (AU)

With this study we try to find out the interaction of sulpiride in tinnitus pathology. This, could help us to control better the tinnitus through tinnitus retraining therapy. MATERIAL AND METHODS: A hundred patients with tinnitus were divided into two groups of 50. Fifty milligrams of sulpiride or placebo were administered for three months, three time per day, with monthly controls. Clinical response, audiometry, tympanometry and acufenometry were registered. RESULTS: In the first month of treatment, only 58% of patients treated with sulpiride improved, and 17% of those treated with placebo, with statistical significance. In the second month, 41% and 20% respectively, and in the third month, 42% and 17% respectively. CONCLUSION: In patients with tinnitus, treatment with sulpiride has improved more than half of them in the first month of treatment. This time is crucial to begin tinnitus retraining therapy and to obtain a greater efficacy (AU)

Evolución de la morfología del reflejo estapedial a lo largo del curso de la otoesclerosis. Reflejo estapedial otoesclerótico provocado / Stapedial reflex evolution in otosclerosis. Provoked otosclerotic stapedial reflex

El reflejo estapedial se viene utilizando, entre otras patologías, para el estudio de la otoesclerosis. En este trabajo retrospectivo hemos reunido 188 historias de pacientes con otoesclerosis confirmada quirúrgicamente y familiares directos de los mismos. Se ha realizado un estudio descriptivo de los estudios audiométricos, timpanometrías y reflejos estapediales ipsilaterales en relación con la fase evolutiva de la otoesclerosis. La hipoacusia de transmisión se ha presentado en el 54%, la hipoacusia mixta en el 29% y la hipoacusia neurosensorial en el 8%. Los reflejos estapediales ON-OFF se han presentado en el 18%, los reflejos invertidos en el 46% y la ausencia de reflejos en el 27%. En las cuatro figuras se recogen los trazados originales de los diferentes tipos de reflejos a lo largo de la evolución de la otoesclerosis: reflejos normales; ON-OFF tipos a, b y c; invertidos a y b; y ausentes. Se correlaciona la fase evolutiva clínica con las audiometrías y los estudios impedanciométricos. Mediante Chi-cuadrado (p<0,001) se ha obtenido significancia estadística en relación con la mayor utilidad de los reflejos estapediales. También se propone la realización del reflejo estapedial provocado en pacientes con otoesclerosis subclínica para desenmascarar la enfermedad. Se concluye que el conocimiento de la morfología evolutiva de los reflejos estapediales en la otoesclerosis ayuda a la capacidad diagnóstica (AU)

Stapedial reflex is used, amongst other pathologies, for the study of otosclerosis. In this retrospective study we have collected 188 cases of patients with otosclerosis whose diagnosis has been confirmed surgically and their first line relatives. We have performed a descriptive analysis of audiometric tests, tympanometries and ipsilateral stapedial reflexes in relation with the evolutive phase of the disease. Transmission hypoacusis has been seen in 54%, mixed hypoacusis in 29% and sensorineural hypoacusis 8% of cases. On and OFF stapedial reflexes have been seen in 18%, inverted reflexes in 46% and absent reflexes in 27% of cases. The original drawings of the different types of reflexes during the evolution of otosclerosis can be seen in the four figures shown in the study: normal reflexes; ON and OFF a, b and c types; inverted a and b; and absent reflexes. The clinical evolutive phase and the audiometric and impedance tests have been correlated. Through Chi-square (p < 0.001), we have obtained a statistical significance in relation to the use of stapedial reflexes. Also it has been suggested the use of provoked stapedial reflexes in patients with sub clinical otosclerosis in order to diagnose the disease. We conclude that the knowledge of the evolutive morphology os stapedial reflexes in otosclerosis helps diagnostic capacity (AU)

Relación de la faringitis crónica con la amigdalectomía mediante estudio microbiológico de cavum / Relationship between chronic pharyngitis and tonsillectomy through microbiological study of cavum

La faringitis crónica es un proceso frecuente y de tratamiento tedioso. Se ha querido poner la faringitis crónica en relación con la intervención quirúrgica de la amigdalectomía. Este estudio consta de un total de 224 pacientes con faringitis crónica, de ellos, 55 amigdalectomizados y 169 no amigdalectomizados. Se ha realizado cultivo microbiológico de cavum en las diferentes estaciones climatológicas. Los gérmenes más frecuentes aislados han sido el Staphylococcus aureus, Corynebacterium sp y Aspergillus. El intervalo de tiempo entre la amigdalectomía y el estudio ha sido de más de 17 años. No se ha encontrado ninguna relación entre la faringitis crónica y la amigdalectomía, considerando los tipos de gérmenes, la estación climatológica anual, el número de gérmenes aislados por cultivo, la tinción de Gram y la edad de los pacientes (AU)

Chronic pharyngitis is an usual process with difficult treatment. It has been related to tonsillectomy. This study collected 224 patients suffering from chronic pharyngitis, 55 tonsillectomies and 169 without operation. Bacteriological culture was done from nasopharynx in the different seasons. Microorganisms more frequent were Staphylococcus aureus, Corynebacterium sp and Aspergillus. The time between the tonsillectomy and this study has been of more than 17 years. No relationship has been found between chronic pharyngitis and tonsillectomy, considering types of microorganisms, seasons, numbers of microorganisms isolated per culture, Gram stain, and age of the patients (AU)

Basófilos de amígdalas palatinas y adenoides en adenoamigdalitis aguda recurrente e hipertrofia adenoamigdalar en niños / Basophils from palatine tonsils and adenoids in recurrent acute adenoid tonsillitis and adenoid tonsillar hypertrophy in children

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Linfocitos de pacientes con sorderas autoinmunitarias presentan hiporreactividad a colágeno tipo II en presencia de la hormona pineal melatonina / Lymphocytes of patients with auto-immune deafness present type II collagen hyporeactivity in the presence of the pineal hormone melatonin

Linfocitos de sangre periférica obtenidos de controles sanos y de pacientes con diversas sorderas mediadas-por mecanismos autoinmunitarios han sido estudiados en presencia de colágeno tipo II y melatonina, activando previamente los linfocitos mediante concanavalina A. Los resultados muestran una hiporreactividad de los linfocitos frente a colágeno tipo II del total de pacientes con sorderas autoinmunes, únicamente cuando los linfocitos se encuentran en presencia de melatonina, con diferencias estadísticamente significativas. Por entidades nosológicas, hay la misma hiporreactividad en la sordera neurosensorial bilateral, enfermedad de Ménière y otoesclerosis. Concluimos que en linfocitos de pacientes con sorderas autoinmunes existe una hiporreactividad frente a colágeno tipo II cuando se compara con linfocitos de controles sanos y que esta hiporreactividad únicamente se pone de manifiesto en presencia de melatonina cuando los linfocitos están activados (AU)

A study was made of the behavior of peripheral blood lymphocytes in healthy controls and patients with various types of hearing loss. Hearing loss of auto-immune origin was studied in the presence and absence of melatonin, activated or not by concanavalin A. In patients with auto-immune hearing loss, lymphocytes showed hyporeactivity to type II collagen in terms of proliferative activity in the presence of concavalin A. Hyporeactivity was especially relevant in melatonin-incubated cells. In different nosologic entities, lymphocyte hyporeactivity to type II collagen was similar in bilateral sensorineural hearing loss, Ménière's disease and otosclerosis. We conclude that the lymphocytes of patients with autoimmune hearing loss showed hyporeactivity to type II collagen when compared to lymphocytes from control subjects. This hyporeactivity was revealed when lymphocytes were activated in the presence of melatonin (AU)