Seguimiento de los pacientes con diabetes tipo 2 durante la pandemia por COVID-19: un estudio multicéntrico en Atención Primaria / Follow-up of patients with type 2 diabetes during the COVID-19 pandemic: A multicentre study in Primary Care

Antecedentes La pandemia de COVID-19 obligó a tomar medidas que implicaban la desatención a los pacientes con diabetes tipo 2 (DM2). Objetivos Explorar la repercusión de la discontinuidad asistencial sobre los pacientes con DM2. Diseño Estudio observacional retrospectivo multicéntrico. Emplazamiento Cinco centros de atención primaria (AP), que no tenían protocolo de actuación específica para ellos, durante 2020 y 2021. Participantes Pacientes con DM2 en Tenerife, Islas Canarias, España. Mediciones principales De las historias clínicas se extrajeron el sexo y la edad, las variables de seguimiento del programa de detección y control de la enfermedad vascular ateroesclerótica (pEVA), de cumplimiento de los objetivos de control y frecuentación al médico de familia y enfermera comunitaria. Resultados Se incluyó a 3.543 pacientes, 1.772 (50%) mujeres, de ellos 2.204 (62%) mayores de 65 años. La gran mayoría de actividades registradas y objetivos de control disminuyeron en 2020, recuperándose en 2021 sin alcanzar los niveles de 2019. En 2020 aumentaron las consultas telefónicas y disminuyeron las presenciales, tendencia mantenida en 2021 para las telefónicas. Las mujeres y los mayores de 65 años presentaron mayor frecuentación, más registros de actividades y logros de objetivos de control en la mayoría de los parámetros. Conclusiones La pandemia supuso una sobrecarga de la AP que ha afectado a la atención de los pacientes con DM2, que no ha logrado restablecerse a los niveles prepandémicos. Los hombres jóvenes conforman la diana de priorización de esta atención. Las medidas antipandémicas han aumentado la consulta telefónica, un recurso que debe potenciarse (AU)

Background The COVID-19 pandemic meant measures had to be taken that implied the neglect of patients with type 2 diabetes (T2D). Objectives to explore the impact of care discontinuity on patients with T2D in Primary Care (PC) centres, who did not have a specific action protocol for them, during 2020 and 2021. Design Multicenter retrospective observational study. Participants Patients with T2D in Tenerife, Canary Islands, Spain. Main Measurements Sex and age, follow-up variables of atherosclerotic vascular disease detection and control programme (pEVA), compliance with the control objectives and visits to the family practitioner and community nurse were extracted from their medical records. Results 3,543 participants took part in the study, 1,772 (50%) women, 2,204 (62%) of whom were older than 65 years of age. The vast majority of registered activities and control objectives decreased in 2020, recovering in 2021 without reaching 2019 levels. In 2020, telephone consultations increased and in-person consultations decreased, a trend that remained unchanged in 2021 for telephone consultations. Women and those over 65 years of age presented higher frequentation, more activity records and achievement of control objectives in most of the parameters. Conclusions The pandemic caused an overload in the PCs that affected the care of patients with T2D, which has not returned to pre-pandemic levels. Young men are the target for prioritization of this care. Anti-pandemic measures have led to an increase in telephone consultations, a resource that should be strengthened (AU)

[Follow-up of patients with type 2 diabetes during the COVID-19 pandemic: A multicentre study in Primary Care]. / Seguimiento de los pacientes con diabetes tipo 2 durante la pandemia por COVID-19: un estudio multicéntrico en Atención Primaria.

BACKGROUND: The COVID-19 pandemic meant measures had to be taken that implied the neglect of patients with type 2 diabetes (T2D). OBJECTIVES: to explore the impact of care discontinuity on patients with T2D in Primary Care (PC) centres, who did not have a specific action protocol for them, during 2020 and 2021. DESIGN: Multicenter retrospective observational study. PARTICIPANTS: Patients with T2D in Tenerife, Canary Islands, Spain. MAIN MEASUREMENTS: Sex and age, follow-up variables of atherosclerotic vascular disease detection and control programme (pEVA), compliance with the control objectives and visits to the family practitioner and community nurse were extracted from their medical records. RESULTS: 3,543 participants took part in the study, 1,772 (50%) women, 2,204 (62%) of whom were older than 65 years of age. The vast majority of registered activities and control objectives decreased in 2020, recovering in 2021 without reaching 2019 levels. In 2020, telephone consultations increased and in-person consultations decreased, a trend that remained unchanged in 2021 for telephone consultations. Women and those over 65 years of age presented higher frequentation, more activity records and achievement of control objectives in most of the parameters. CONCLUSIONS: The pandemic caused an overload in the PCs that affected the care of patients with T2D, which has not returned to pre-pandemic levels. Young men are the target for prioritization of this care. Anti-pandemic measures have led to an increase in telephone consultations, a resource that should be strengthened.

Expression of brain-derived neurotrophic factor protein in the adult rat central nervous system.

We have generated and characterized a multi-functional polyclonal anti-brain-derived neurotrophic factor antibody. Western blot analysis, dorsal root ganglion neurite outgrowth and dorsal root ganglion neuron survival assays showed that this antibody specifically recognized brain-derived neurotrophic factor and not the other neurotrophins. Furthermore, it was capable of blocking the functional effects of brain-derived neurotrophic factor. Using this antibody, we examined the expression of brain-derived neurotrophic factor in adult rat brains by immunohistochemistry. We found distinct brain-derived neurotrophic factor immunoreactivity in several structures of the brain. These included the neocortex, piriform cortex, amygdaloid complex, hippocampal formation, claustrum, some thalamic and hypothalamic nuclei, the substantia nigra and some brainstem structures. In contrast to brain-derived neurotrophic factor messenger RNA expression, brain-derived neurotrophic factor immunoreactivity was also found in the lateral septum, bed nucleus of the stria teminalis, medial preoptic nucleus, olivery pretectal nucleus, lateral paragigantocellular nucleus and the dorsal horn of the spinal cord. In normal adult rat brains, there was little or no staining in the CA1 region or the granule cell layer of the dentate gyrus of the hippocampus. However, kainate treatments greatly increased brain-derived neurotrophic factor immunoreactivity in the pyramidal cells of the CA1 region, as well as in the dentate gyrus, CA2 and CA3 hippocampal regions. We present evidence for both the subcellular localization and anterograde transport of endogenous brain-derived neurotrophic factor in the central nervous system. The detection of brain-derived neurotrophic factor protein in several discrete regions of the adult brain, and brain-derived neurotrophic factor's dramatic up-regulation following kainate treatment, strongly supports a role of brain-derived neurotrophic factor in the maintenance of adult neurons and synapses. Since several populations of neurons lost during neurodegenerative diseases synthesize brain-derived neurotrophic factor protein, modulation of brain-derived neurotrophic factor levels may be clinically beneficial. The antibody described in this paper will be helpful in determining more precisely the functional activities of brain-derived neurotrophic factor in the adult.

In vivo neurotrophic effects of GDNF on neonatal and adult facial motor neurons.

Motor neurons require neurotrophic factor(s) for their survival during development and for maintenance of function in adulthood. In vivo studies have shown that motor neurons respond to a variety of molecules, including ciliary neurotrophic factor, members of the neurotrophin family, and the insulin growth factor IGF-1 (refs 3-13). Here we investigate the potential motor neuron neurotrophic effects of glial-cell-line-derived neurotrophic factor (GDNF), initially identified as a neurotrophic factor for substantia nigra dopaminergic neurons. We find that GDNF is retrogradely transported, in a receptor-mediated fashion, by spinal cord motor neurons in neonatal rats. Local application of GDNF to the transected facial nerve prevents the massive motor neuron cell death and atrophy that normally follows axotomy in the neonatal period. In adult rats, GDNF administered locally or systemically can markedly attenuate the lesion-induced decrease of choline acetyltransferase immunoreactivity in the facial nucleus. Our data indicate that GDNF has very profound neurotrophic effects in vivo on developing as well as on adult motor neurons, and is the most potent motor neuron trophic factor found so far.

Serotonin 5-HT3 antagonists fail to affect ethanol self-administration of rats.

Five Long-Evans hooded rats were trained to lever press according to fixed-ratio 5 reinforcement schedules for 0.06 ml dipper deliveries of 8% w/v ethanol during daily (M-F) 0.5-h experimental sessions. After ethanol self-administration was established, doses of the serotonin 5-HT3 antagonists, ondansetron (0.03-3.0 mg/kg), granisetron (0.01-1.0 mg/kg), and SC-51296 (0.1-10.0 mg/kg) were administered prior to ethanol sessions to determine their effects on ethanol self-administration. None of the doses of the antagonists had significant effects on numbers of obtained ethanol deliveries. Subsequently, each antagonist (ondansetron, 0.1 mg/kg; granisetron, 0.3 mg/kg; SC-51296, 0.1 mg/kg) was administered b.i.d. for five consecutive daily sessions. During none of these chronic tests with the 5-HT3 antagonists were there significant main effects of drug administration. Overall, these results do not support the hypothesis that the serotonin 5-HT3 antagonists would have robust therapeutic efficacy in the treatment of alcoholism.

The biological responses of axotomized adult motoneurons to brain-derived neurotrophic factor.

Recent studies showed that brain-derived neurotrophic factor (BDNF) prevents developing motoneurons from naturally occurring and axotomy-induced cell death. Here we examined whether adult motoneurons retain responsiveness to BDNF. Consistent with previous studies, we found that adult spinal and brainstem motoneurons expressed the mRNA of BDNF receptor, trkB. In addition, the trkB immunoreactivities were readily detected in the adult spinal and brainstem motoneurons. We then demonstrated that axotomized adult motoneurons responded to exogenous BDNF. BDNF administered locally markedly attenuated the lesion-induced decrease of ChAT immunoreactivity and activity and enhanced the lesion-induced reexpression of low-affinity NGF receptor immunoreactivity in adult facial motoneurons. Furthermore, we found BDNF administered subcutaneously, intravenously, and into the cerebral ventricle attenuated the lesion-induced decrease of ChAT immunoreactivity in adult facial motoneurons in a dose-dependent fashion. Our data indicate that adult motoneurons retain their responsiveness to BDNF, suggesting that BDNF may be useful as a therapeutic agent for adult motoneuron disease.

Assessment of long-term effects of transient anoxia on metabolic activity of rat hippocampal slices using triphenyltetrazolium chloride.

Hippocampal slices maintained in an oxygen-rich static interface chamber remained viable, as determined by the mitochondrial marker 2,3,5-triphenyltetrazolium chloride (TTC), for over 20 h in vitro. By contrast, slices exposed, after 1 h in vitro, to an anoxic environment for 25 min and then allowed to recover for 1-18 h, showed an initial slight decrease in TTC staining followed by a dramatic decrease at time points greater than 6.5 h after anoxia. These data are suggestive of delayed neuronal death. Furthermore, the decreases in TTC staining induced by anoxia could be prevented by conditions known to prevent cell death either in vitro or in vivo. For example, pretreatment of the slices with the N-methyl-D-aspartate antagonist 3-((RS)-2-carboxy-piperazin-4-yl)-propyl-1- phosphonic acid dose-dependently prevented the loss of TTC staining induced by 25 min anoxia. In addition, high-intensity TTC staining correlated with normal CA1 synaptic activity, even after more than 20 h in vitro, suggesting that TTC staining reflects functional neuronal activity. These data suggest that the use of TTC staining of in vitro hippocampal slices may represent a novel and convenient screen for anti-ischemic compounds.

Phencyclidine established as a discriminative stimulus using ethanol as a reinforcer.

Long-Evans hooded rats were initially trained to lever press, in standard, operant conditioning chambers, according to a fixed-ratio 1 (FR1) reinforcement schedule using 0.06ml deliveries of 8% w/v ethanol as the reinforcer, during daily Monday-Friday, 1h experimental sessions. Next, experimental sessions were reduced to 0.5h, the FR value was increased to 5, and the rats were trained to discriminate 2.0mg/kg s.c. phencyclidine (PCP) from saline vehicle using standard, drug discrimination training procedures, with 8% ethanol as the reinforcer. Following training, dose-response tests with PCP (0.1-4.0mg/kg), ketamine (0.1-18mg/kg), dexoxadrol (1.0-5.6mg/kg) and morphine (1.0-9.0mg/kg) were conducted. More PCP-lever presses were emitted than saline-lever presses at several doses of PCP, ketamine, and dexoxadrol, indicating generalization from the 2.0mg/kg PCP stimulus. When morphine was tested, more saline-lever than PCP-lever presses were made, and percent PCP-lever pressing never exceeded an average of 12% at any dose tested. This study demonstrates that one drug of abuse, PCP, can serve as a discriminative stimulus when another drug of abuse, ethanol, serves as the reinforcing stimulus, and is the first explicit laboratory demonstration of drug discriminative stimulus control during drug self-administration.

Analogs of the delta opioid receptor selective cyclic peptide [2-D-penicillamine,5-D-penicillamine]-enkephalin: 2',6'-dimethyltyrosine and Gly3-Phe4 amide bond isostere substitutions.

In order to develop systemically-active opioid peptides, the delta-selective, opioid pentapeptide [D-Pen2,D-Pen5]-enkephalin (DPDPE) was modified by esterification and by substitution of 2',6'-dimethyltyrosine for tyrosine to yield 4. Compound 4 was on the order of 8- and 800-fold more active than DPDPE in both delta and mu opioid radioligand binding assays, respectively, in rat neural membrane suspensions. Compound 4 was considerably more potent than DPDPE at inhibiting contractions of electrically-stimulated mouse vas deferens in vitro, and this effect was very sensitive to naltrindole, a delta-selective opioid antagonist. These observations can be taken as indication that 4 exerts its effects through delta opioid receptors. This interpretation is supported by the finding that the EC50 value of 4 derived in the smooth muscle assay is very similar to that derived in NG108-15 neuroblastoma cells, a preparation devoid of mu receptors. Unlike DPDPE, 4 exhibited significant, naloxone-sensitive, antinociceptive activity when administered systemically, as measured by inhibition of phenylbenzquinone-induced stretching in mice (ED50 = 2.1 mg/kg). Compound 4 also displayed significant antinociceptive activity following systemic administration as measured by its action in mice to increase latencies for tail withdrawal from radiant heat (ED50 = 50 mg/kg). Compound 4 did not produce morphine-like discriminative stimulus effects in rats trained to discriminate 3.0 mg/kg morphine from vehicle at doses ranging from 30 to 120 mg/kg. This observation can be interpreted as indication that within this dosage range there is an absence of morphine-like subjective effects. Physical dependence, however, could be induced in mice at higher doses of 4 under a progressively-graded, 4-day dose regimen. Congeners of 4 with amide bond surrogates for the Gly-Phe amide bond (oxymethylene, trans-double bond, and bismethylene isosteres) in the cyclic core of DPDPE were prepared in an attempt to increase the antinociceptive activity of 4. While some of the congeners were active in the in vitro assays, they did not display significant antinociceptive activity following systemic administration. The preparation of all the compounds was accomplished by solution-phase methods. The mechanisms which might underlie the biological and systemic activity of 4 are discussed.