Immune thrombotic thrombocytopenic purpura in older patients: Results from the Spanish TTP Registry (REPTT).

Immune thrombotic thrombocytopenic purpura (iTTP) is an ultra-rare disease that seldom occurs in the elderly. Few reports have studied the clinical course of iTTP in older patients. In this study, we have analysed the clinical characteristics at presentation and response to therapy in a series of 44 patients with iTTP ≥60 years at diagnosis from the Spanish TTP Registry and compared them with 209 patients with <60 years at diagnosis from the same Registry. Similar symptoms and laboratory results were described in both groups, except for a higher incidence of renal dysfunction among older patients (23% vs. 43.1%; p = 0.008). Front-line treatment in patients ≥60 years was like that administered in younger patients. Also, no evidence of a difference in clinical response and overall survival was seen in both groups. Of note, 14 and 25 patients ≥60 years received treatment with caplacizumab and rituximab, respectively, showing a favourable safety and efficacy profile, like that observed in patients <60 years.

Acute and chronic stress increase salivary cortisol: a study in the real-life setting of a national examination undertaken by medical graduates.

Spanish medical graduates who apply for a medical specialty training position (MIR) must take an examination that will shape their future personal and professional lives. Preparation for the test represents an important stressor that persists for several months. The aim of this study was to elucidate the stress pattern of this group and evaluate possible changes in the circadian rhythm of cortisol release in medical graduates preparing for this test. A repeated-measures longitudinal study was performed, measuring the salivary cortisol concentrations in 36 medical graduates (13 males and 23 females; mean age of 24.2 years) on five sampling days. Five cortisol samples were collected from 07:00 to 21:00 h in order to monitor changes in the circadian rhythm. On all sampling days (except on the day of the official examination), anxiety and psychological stress were evaluated with the Spanish versions of the State-Trait Anxiety Inventory (STAI) and the Perceived Stress Scale (PSS). During the study period, participants showed higher levels of anxiety than the Spanish reference population as well as a progressive increase in self-perceived stress. A significant increase in salivary cortisol concentration was observed in both chronic (study and examination preparation) and acute (examinations) situations. Our results suggest that the cortisol awakening response (CAR) may be a good indicator of anticipatory stress but is unaffected by long-term examination preparation. Comparison of results between the official examination day and the mock examination days yielded evidence that learning may modulate the behavior of the hypothalamic-pituitary-adrenal axis.

Sampling methodologies for epidemiologic surveillance of men who have sex with men and transgender women in Latin America: an empiric comparison of convenience sampling, time space sampling, and respondent driven sampling.

Alternatives to convenience sampling (CS) are needed for HIV/STI surveillance of most-at-risk populations in Latin America. We compared CS, time space sampling (TSS), and respondent driven sampling (RDS) for recruitment of men who have sex with men (MSM) and transgender women (TW) in Lima, Peru. During concurrent 60-day periods from June-August, 2011, we recruited MSM/TW for epidemiologic surveillance using CS, TSS, and RDS. A total of 748 participants were recruited through CS, 233 through TSS, and 127 through RDS. The TSS sample included the largest proportion of TW (30.7 %) and the lowest percentage of subjects who had previously participated in HIV/STI research (14.9 %). The prevalence of newly diagnosed HIV infection, according to participants' self-reported previous HIV diagnosis, was highest among TSS recruits (17.9 %) compared with RDS (12.6 %) and CS (10.2 %). TSS identified diverse populations of MSM/TW with higher prevalences of HIV/STIs not accessed by other methods.

A simple mathematical model that describes the growth of the area and the number of total and viable cells in yeast colonies.

UNLABELLED: We propose a model, based on the Gompertz equation, to describe the growth of yeasts colonies on agar medium. This model presents several advantages: (i) one equation describes the colony growth, which previously needed two separate ones (linear increase of radius and of the squared radius); (ii) a similar equation can be applied to total and viable cells, colony area or colony radius, because the number of total cells in mature colonies is proportional to their area; and (iii) its parameters estimate the cell yield, the cell concentration that triggers growth limitation and the effect of this limitation on the specific growth rate. To elaborate the model, area, total and viable cells of 600 colonies of Saccharomyces cerevisiae, Debaryomyces fabryi, Zygosaccharomyces rouxii and Rhodotorula glutinis have been measured. With low inocula, viable cells showed an initial short exponential phase when colonies were not visible. This phase was shortened with higher inocula. In visible or mature colonies, cell growth displayed Gompertz-type kinetics. It was concluded that the cells growth in colonies is similar to liquid cultures only during the first hours, the rest of the time they grow, with near-zero specific growth rates, at least for 3 weeks. SIGNIFICANCE AND IMPACT OF THE STUDY: Mathematical models used to predict microbial growth are based on liquid cultures data. Models describing growth on solid surfaces, highlighting the differences with liquids cultures, are scarce. In this work, we have demonstrated that a single Gompertz equation describes accurately the increase of the yeast colonies, up to the point where they reach their maximum size. The model can be used to quantify the differences in growth kinetics between solid and liquid media. Moreover, as all its parameters have biological meaning, it could be used to build secondary models predicting yeast growth on solid surfaces under several environmental conditions.

Integrated screening and testing for TB and COVID-19 in Peru.

We describe the experience of integrating COVID-19 screening and testing into a mobile TB screening unit in Lima, Peru. All attendees received chest radiographs, which were analysed using CAD4TB and CAD4COVID; Xpert MTB/RIF Ultra was used to test for TB, and antibody and polymerase chain reaction (PCR) for SARS-CoV-2. One Xpert-positive TB case was diagnosed per 168 people screened, one person with SARS-CoV-2 antibodies per 3 people screened, and one PCR-confirmed SARS-CoV-2 infection per 8 people screened. Integrated screening can help to avoid delays in the diagnosis of both TB and COVID-19.

Nous décrivons l'expérience de l'intégration du dépistage et du test COVID-19 dans une unité mobile de dépistage de la TB à Lima, au Pérou. Toutes les personnes présentes ont reçu des radiographies pulmonaires, qui ont été analysées à l'aide de CAD4TB et CAD4COVID ; Xpert® MTB/RIF Ultra a été utilisé pour le dépistage de la TB, et les anticorps et la réaction en chaîne par polymérase (PCR) pour le SARS-CoV-2. Un cas de TB Xpert-positif a été diagnostiqué pour 168 personnes dépistées, une personne présentant des anticorps du SARS-CoV-2 pour 3 personnes dépistées et une infection du SARS-CoV-2 confirmée par PCR pour 8 personnes dépistées. Le dépistage intégré peut contribuer à éviter les retards dans le diagnostic de la TB et du COVID-19.

Using digital chatbots to close gaps in healthcare access during the COVID-19 pandemic.

INTRODUCTION: Chatbots have emerged as a first link to care in recent years. The COVID-19 pandemic, and consequent health system disruptions, expanded their use. Socios En Salud (SES) introduced chatbots in Peru, which experienced one of the highest excess COVID mortalities in the world. METHODS: SES and the government identified unmet population health needs, which could be amenable to virtual interventions. Chatbots were developed to screen individuals for these conditions; we describe the period of deployment, number of screenings, and number of people who received services. RESULTS: Between April 2020 and May 2021, SES deployed nine ChatBots: four for mental health, two for maternal and child health, and three for chronic diseases: breast cancer, hypertension, diabetes mellitus, and obesity. Mental health services were provided to 42,932 people, 99.99% of those offered services. The other ChatBots reached fewer people. Overall, more than 50% of eligible people accepted chatbot-based services. DISCUSSION: ChatBot use was highest for mental health. Chatbots may increase connections between a vulnerable population and health services; this is likely dependent on several factors, including condition, population, and penetration of smart phones. Future research will be critical to understand user experience and preferences and to ensure that chatbots link vulnerable populations to appropriate, high-quality care.

INTRODUCTION: Les chatbots se sont imposés comme un premier lien aux soins ces dernières années. La pandémie de COVID-19, et les perturbations du système de santé qui en ont résultées, ont élargi leur champ d'application. Socios En Salud (SES) a introduit les chatbots au Pérou, qui a connu l'une des surmortalités dues au COVID les plus élevées au monde. MÉTHODES: SES et le gouvernement ont identifié des besoins non satisfaits en matière de santé de la population, qui pourraient faire l'objet d'interventions virtuelles. Des chatbots ont été développés pour dépister des individus pour ces conditions ; nous décrivons la période de leur déploiement, le nombre de dépistages et le nombre de personnes qui ont reçu ces services. RÉSULTATS: Entre avril 2020 et mai 2021, SES a déployé neuf ChatBots : quatre pour la santé mentale, deux pour la santé maternelle et infantile et trois pour les maladies chroniques, comme le cancer du sein, l'hypertension, le diabète et l'obésité. Des services de santé mentale ont été fournis à 42 932 personnes, soit 99,99% des personnes proposées. Les autres ChatBots ont touché moins de personnes. Dans l'ensemble, plus de 50% des personnes éligibles ont accepté les services proposés par les chatbots. DISCUSSION: L'utilisation des ChatBots était la plus élevée pour la santé mentale. Les chatbots peuvent augmenter les connexions entre une population vulnérable et les services de santé, mais cela dépende de plusieurs facteurs, dont la condition, la type de population et la pénétration des smartphones. Les recherches futures seront essentielles pour comprendre l'expérience et les préférences des utilisateurs et pour s'assurer que les chatbots relient les populations vulnérables vulnérables aux soins appropriés et de qualité.

Analysis of serious non-AIDS events among HIV-infected adults at Latin American sites.

OBJECTIVE: Acquired immune deficiency appears to be associated with serious non-AIDS (SNA)-defining conditions such as cardiovascular disease, liver and renal insufficiency and non-AIDS-related malignancies. We analysed the incidence of, and factors associated with, several SNA events in the LATINA retrospective cohort. MATERIALS AND METHODS: Cases of SNA events were recorded among cohort patients. Three controls were selected for each case from cohort members at risk. Conditional logistic models were fitted to estimate the effect of traditional risk factors as well as HIV-associated factors on non-AIDS-defining conditions. RESULTS: Among 6007 patients in follow-up, 130 had an SNA event (0.86 events/100 person-years of follow-up) and were defined as cases (40 with cardiovascular events, 54 with serious liver failure, 35 with non-AIDS-defining malignancies and two with renal insufficiency). Risk factors such as diabetes, hepatitis B and C virus coinfections and alcohol abuse showed an association with events, as expected. The last recorded CD4 T-cell count prior to index date (P = 0.0056, with an average difference of more than 100 cells/µL) and area under the CD4 cell curve in the year previous to index date (P = 0.0081) were significantly lower in cases than in controls. CD4 cell count at index date was significantly associated with the outcome after adjusting for risk factors. CONCLUSIONS: The incidence and type of SNA events found in this Latin American cohort are similar to those reported in other regions. We found a significant association between immune deficiency and the risk of SNA events, even in patients under antiretroviral treatment.

Identification and characterization of two novel (neuro)endocrine long coiled-coil proteins.

We have identified a novel vertebrate-specific gene by applying a Differential Display method on two distinct subtypes of pituitary melanotropes showing divergent secretory phenotypes of hypo- and hypersecretion. A paralogue of this gene was also identified. The existence of a long coiled-coil domain and a C-terminal transmembrane domain in the sequences, together with the Golgi distribution of the proteins in transfected cells, suggest that they can be considered as new members of the golgin family of proteins. Both genes were primarily expressed in (neuro)endocrine tissues in vertebrates thus supporting a role for these proteins in the regulated secretory pathway.

A mesoscopic stochastic model for the specific consumption rate in substrate-limited microbial growth.

The specific consumption rate of substrate, as well as the associated specific growth rate, is an essential parameter in the mathematical description of substrate-limited microbial growth. In this paper we develop a completely new kinetic model of substrate transport, based on recent knowledge on the structural biology of transport proteins, which correctly describes very accurate experimental results at near-zero substrate concentration values found in the literature, where the widespread Michaelis-Menten model fails. Additionally, our model converges asymptotically to Michaelis-Menten predictions as substrate concentration increases. Instead of the single active site enzymatic reaction of Michaelis-Menten type, the proposed model assumes a multi-site kinetics, simplified as an apparent all-or-none mechanism for the transport, which is controlled by means of the local substrate concentration in the close vicinity of the transport protein. Besides, the model also assumes that this local concentration is not equal to the mean substrate concentration experimentally determined in the culture medium. Instead, we propose that it fluctuates with a mostly exponential distribution of Weibull type.

Differential expression and processing of chromogranin A and secretogranin II in relation to the secretory status of endocrine cells.

Chromogranin A (CgA) and secretogranin II (SgII) are neuroendocrine secretory proteins that participate in regulation of the secretory pathway and also serve as precursors of biologically active peptides. To investigate whether there is a relationship between the expression, distribution, and processing of CgA and SgII and the degree of secretory activity, we employed two melanotrope subpopulations of the pituitary intermediate lobe that exhibit opposite secretory phenotypes. Thus, although one of the melanotrope subtypes shows high secretory activity, the other exhibits characteristics of a hormone storage phenotype. Our data show that SgII expression levels were higher in secretory melanotropes, whereas CgA expression showed similar rates in both cell subsets. The use of various antibodies revealed the presence of the unprocessed proteins as well as three CgA-derived peptides (67, 45, and 30 kDa) and six SgII-derived peptides (81, 66, 55, 37, 32, and 30 kDa) in both subpopulations. However, the smallest molecular forms of both granins predominated in secretory melanotropes, whereas the largest SgII- and CgA-immunoreactive peptides were more abundant in storage melanotropes, which is suggestive of a more extensive processing of granins in the secretory subset. Confocal microscopy studies showed that CgA immunoreactivity was higher in storage cells, but SgII immunoreactivity was higher in secretory melanotropes. Taken together, our results indicate that SgII and CgA are differentially regulated in melanotrope subpopulations. Thus, SgII expression is strongly related to the secretory activity of melanotrope cells, whereas CgA expression may not be related to secretory rate, but, rather, to hormone storage in this endocrine cell type.

Cortistatin mimics somatostatin by inducing a dual, dose-dependent stimulatory and inhibitory effect on growth hormone secretion in somatotropes.

Cortistatin is a recently discovered neuropeptide that is structurally related to somatostatin, the classic inhibitor of growth hormone (GH) release. Cortistatin binds with high affinity to all five somatostatin receptors (sst1-5), and, like somatostatin, cortistatin inhibits in vivo GH release in man and rats. In this report, we compared the in vitro actions of cortistatin and somatostatin using primary pig pituitary cell cultures. In this species, we have previously reported that somatostatin not only inhibits GH-releasing hormone (GHRH)-stimulated GH release at high doses, but also stimulates basal GH release at low (pM) doses, a dual response that is markedly dependent on the subpopulation of pituitary somatotropes examined. Results reported herein demonstrate that cortistatin closely mimics the dose-dependent inhibitory and stimulatory effects of somatostatin on GH secretion. As cortistatin, unlike somatostatin, binds to the human receptor for ghrelin/GH secretagogs (GHS-R), we also investigated whether cortistatin stimulates GH release through this receptor by using a synthetic, short form of cortistatin, cortistatin-8 (CST8), which lacks the sst-binding capacity of full-length cortistatin but retains its GHS-R-binding capacity. Interestingly, CST8 stimulated GH release only at low doses (10(-15) M), and did not reduce GH secretion stimulated by GHRH, ghrelin, or low-dose, full-length cortistatin, yet it counteracted that induced by a nonpeptidyl GHS, L-163 255. Taken together, our results indicate that the dual, inhibitory and stimulatory effects of cortistatin on GH release closely parallel those of somatostatin and are probably mediated by the same receptor(s) and signaling pathway(s) for both peptides. Furthermore, they suggest that the pathway(s) activated by cortistatin (and somatostatin) to stimulate GH release are not initiated by GHS-R activation.

Ecotoxicological effects of metal pollution in two mollusc species from the Spanish South Atlantic littoral.

Metal accumulation and some of their biochemical effects have been studied in oysters (Crassostrea angulata) and mussels (Mytilus galloprovincialis) of the South Atlantic Spanish littoral. Especial attention has been paid to antioxidant defences and oxidative damage to biomolecules. Deep differences in the response of oysters and mussels to metal pollution were found. Oysters, with the higher metal loads of both species, showed increased antioxidant defences, and less extensive oxidative damage. In contrast, mussels, which accumulated much lower metal concentrations, showed clear increases in oxidized biomolecules, in agreement with their low increases in the antioxidant defence mechanisms. Our results suggest that mussels are more sensitive and less well adapted to metal pollution, probably explaining their absence in the most contaminated studied site, Mazagón. We conclude that oysters can be used as more sensitive bioindicator of pollution in the South Spanish littoral, and as a suitable model to study the adaptation to metal pollution.

Growth kinetics and physiological behavior of co-cultures of Saccharomyces cerevisiae and Kluyveromyces lactis, fermenting carob sugars extracted with whey.

Alcoholic fermentation of carob waste sugars (sucrose, glucose and fructose) extracted with cheese whey, by co-cultures of Saccharomyces cerevisiae and Kluyveromyces lactis has been analyzed. Growth and fermentation of S. cerevisiae in the carob-whey medium showed an inhibition of about 30% in comparison with water-extracted carob. The inhibition of K. lactis on carob-whey was greater (70%) when compared with the whey medium alone, due to osmolarity problems. Oxygen availability was a very important factor for K. lactis, influencing its fermentation performance. When K. lactis was grown alone on carob-whey medium, lactose was always consumed first, and glucose and fructose were consumed afterwards, only at high aeration conditions. In co-culture with S. cerevisiae, K. lactis was completely inhibited and, at low aeration, died after 3 days; at high aeration this culture could survive but growth and lactose fermentation were only recovered after S. cerevisiae became stationary. To overcome the osmolarity and K. lactis' oxygen problems, the medium had to be diluted and a sequential fermentative process was designed in a STR-3l reactor. K. lactis was inoculated first and, with low aeration (0.13vvm), consumed all the lactose in 48h. Then S. cerevisiae was inoculated, consuming the total of the carob sugars, and producing ethanol in a fed-batch regime. The established co-culture with K. lactis increased S. cerevisiae ethanol tolerance. This fermentation process produced ethanol with good efficiency (80g/l final concentration and a conversion factor of 0.4g ethanol/g sugar), eliminating all the sugars of the mixed waste. These efficient fermentative results pointed to a new joint treatment of agro-industrial wastes which may be implemented successfully, with economic and environmental sustainability for a bioethanol industrial proposal.

Reversible loss of affinity induced by glucose in the maltose-H+ symport of Saccharomyces cerevisiae.

Glucose represses and inactivates maltose transport in Saccharomyces cerevisiae. The inactivation has been described as an irreversible process involving proteolysis. We have studied the inactivation of the maltose-H+ symport in this yeast and have observed that the mechanism of inactivation depends on the physiological conditions. In resting cells there was a decrease in transport capacity. The rate of decrease was enhanced nonspecifically by the presence of a sugar, glucose being more effective than maltose. In growing cells, glucose induced a decrease in affinity of the H+-symport which could be recovered by starvation, even in the presence of cycloheximide; there was no loss in capacity or, if present, this loss could be explained fully by the dilution due to repression during growth on glucose. We submit that in growing cells inactivation consists in a reversible modification of the permease not involving proteolysis.

Effect of starvation on lipoprotein lipase activity in the liver of developing rats.

Liver lipoprotein lipase activity in neonatal (1- and 5-day-old) rats was 2-3-times than in the liver of adult rats. In mid-suckling (15-day-old) or weaned (30-day-old) animals, it was not significantly different from the low activity detected in adult rats. Starvation resulted in a 3-fold increase of lipoprotein lipase activity in the neonatal liver, but did not affect the activity in the liver of mid-suckling, weaned or adult rats. When isolated livers from both 1- and 5-day-old pups were perfused with heparin, a sharp peak of lipoprotein lipase activity appeared in the perfusate. In fed neonates, the peak area accounted for about 70% of the total (released + non-releasable) activity. In starved neonates, the proportion of heparin-releasable activity increased up to about 90%. These results indicate that neonatal rat liver lipoprotein lipase activity is markedly affected by changes in the nutritional status of the animal, and the effect is restricted to the vascular pool of the enzyme, as was reported in extrahepatic tissues from adult rats.

Analysis of Rab18 and a new golgin in the secretory pathway.

Two new amphibian genes have been isolated and characterized from frog melanotropes, and the level of expression of these genes is related to the secretory status of the cells. Both genes, Rab18 and a novel member of the golgin family of proteins, are ubiquitously expressed in endocrine and nonendocrine tissues, and their corresponding proteins appear to show intracellular distributions associated with discrete vesicular and tubular structures, respectively, suggesting that they may play relevant roles in the regulation of the secretory pathway.

A model of the specific growth rate inhibition by weak acids in yeasts based on energy requirements.

Zygosaccharomyces bailii, a spoilage yeast, capable of metabolic activity in food environments with low pH, low a(w) and in the presence of weak acid preservatives was chosen for a study on the effect of benzoic acid on growth parameters. In batch cultures, under controlled pH, this food preservative inhibited growth, decreasing the specific growth rate (mu) and the yield coefficient (Y(S)) on glucose. Data obtained at pH 3.5, 4.0 and 4.5 showed that this inhibition was exclusively promoted by the undissociated form of the acid since the effect was independent of pH when the concentration of the acid was expressed in this form. Moreover, the relationship between the values for mu and Y(S), provided evidence that the specific consumption rate of glucose (q(S)) was not affected by benzoic acid, indicating that the inhibition of growth should be completely explained by a decrease of Y(S). The outcome of parallel experiments performed in continuous culture was that the decrease of Y(S) was due to an increase of the maintenance coefficient (m), defined as the fraction of q(S) diverted from growth to cope with stress, represented in this case by the presence of the preservative. Based on these results a model was built, assuming that m increased hyperbolically with the concentration of benzoic acid, from zero in the absence of the acid up to q(S) when growth was completely inhibited. The concentration of the acid, for which m=q(S)/2, is a constant (K(W)), and represents a measure of the tolerance for a preservative, in this case benzoic acid. The simple equation mu/mu(0)=1+W/K(W) predicts the value of mu for a concentration (W) of the preservative, requiring the knowledge of two parameters: the specific growth rate in the absence of the preservative (mu(0)) and K(W). The equation fitted very well the data of the effect of benzoic acid on the specific growth rate of Z. bailii, having K(W)=0.96 mM benzoic acid. The model was also validated with other spoilage yeasts grown in the presence of benzoic acid in microtiter plates in an automated spectrophotometer. The values obtained for K(W) under these conditions confirm Z. bailii as the most tolerant (K(W)=2.1 mM) followed by Pichia sp. (K(W)=0.78 mM), Saccharomyces cerevisiae (K(W)=0.53 mM) and Debaryomyces hansenii (K(W)=0.11 mM).

Kinetic and Energetic Parameters of Carob Wastes Fermentation by Saccharomyces cerevisiae: Crabtree Effect, Ethanol Toxicity, and Invertase Repression.

Carob waste is a useful raw material for the second-generation ethanol because 50% of its dry weight is sucrose, glucose, and fructose. To optimize the process, we have studied the influence of the initial concentration of sugars on the fermentation performance of Saccharomyces cerevisiae. With initial sugar concentrations (S0) of 20 g/l, the yeasts were derepressed and the ethanol produced during the exponential phase was consumed in a diauxic phase. The rate of ethanol consumption decreased with increasing S0 and disappeared at 250 g/l when the Crabtree effect was complete and almost all the sugar consumed was transformed into ethanol with a yield factor of 0.42 g/g. Sucrose hydrolysis was delayed at high S0 because of glucose repression of invertase synthesis, which was triggered at concentrations above 40 g/l. At S0 higher than 250 g/l, even when glucose had been exhausted, sucrose was hydrolyzed very slowly, probably due to an inhibition at this low water activity. Although with lower metabolic rates and longer times of fermentation, 250 g/l is considered the optimal initial concentration because it avoids the diauxic consumption of ethanol and maintains enough invertase activity to consume all the sucrose, and also avoids the inhibitions due to lower water activities at higher S0.

Melanotrope cell plasticity: a key mechanism for the physiological adaptation to background color changes.

The intermediate lobe of the pituitary secretes the melanotropic hormone alpha-MSH, which in amphibians plays a crucial role in skin color adaptation. It has been previously demonstrated that, in the frog Rana ridibunda, the intermediate lobe is composed of two distinct subpopulations of melanotrope cells that can be separated in vitro by using Percoll density gradients. These two melanotrope cell subsets, referred to as high-density (HD) and low-density (LD) cells, differ in their ultrastructural characteristics as well as in their biosynthetic and secretory activity. However, the specific, physiological role of the heterogeneity displayed by melanotrope cells remains elusive. In the present study, we investigated the effects of background color adaptation on melanotrope cell subpopulations. We found that adaptation of frogs to dark or white environment did not modify either the overall number of cells per intermediate lobe or the apoptotic and proliferation rates of melanotrope cells. On the other hand, adaptation of the animals to a white background significantly increased the proportion of hormone-storage HD cells and caused a concomitant decrease in that of LD cells (which exhibit higher levels of alpha-MSH release and POMC messenger RNA than HD cells). Conversely, after black-background adaptation the proportion of LD cells was markedly increased, suggesting that interconversion of HD cells to LD cells occurs during physiological activation of the intermediate lobe. In addition, black-background adaptation also enhanced alpha-MSH release by both cell subpopulations and increased inositol phosphate production in LD cells. These data indicate that, in frog, the proportions of the two melanotrope cell subsets undergo marked modifications during skin color adaptation, likely reflecting the occurrence of a secretory cell cycle whose dynamics are highly correlated to the hormonal demand imposed by the environment.