An epidemiological evaluation of COVID-19 in La paz, Bolivia.

INTRODUCTION: The Plurinational State of Bolivia (Bolivia) has experienced four major waves of coronavirus disease 2019 (COVID-19) so far. Although the ministry of health has been tracking morbidity and mortality through each wave, epidemiology of COVID-19 in Bolivia is not well defined, despite a need for more accurate measurement of the number of cases and deaths to allow for forecasting of the pandemic. This study examined prevalence of COVID-19 at community level, determinants of its occurrence and vaccine effectiveness. METHODS: We conducted a cross-sectional study in La Paz city on 2,775 individuals between March 2020 and February 2022. A structured questionnaire was used to collect data on COVID-19 morbidity, mortality and vaccination status. RESULTS: Of the 2,775 participants, 1,586 (57.1%) were infected with COVID-19, and 187 (6.7%) were suspected cases. The mortality rate was 2.9%. Sinopharm, Johnson & Johnson, Gamaleya, Pfizer-BioNtech, Moderna and AstraZeneka vaccines are in use, and all vaccines have demonstrated effectiveness in reducing the risk of onset. Risk for mortality was significantly lower in the vaccinated group with an odds ratio of 0.037 (95％ confidential interval: 0.01-0.10, p-value: <0.001). CONCLUSIONS: Actual prevalence of COVID-19 in La Paz (the prevalence rate: 63.8%, including suspected case) was higher than that reported by the Ministry of Health and Sports in Bolivia (7.5%). In addition, vaccination has contributed significantly to the control of the COVID-19 epidemic in Bolivia. We believe that our report will be useful for COVID-19 prevention strategies in Bolivia for the future.

Macrophages are activated in the rat anterior pituitary under chronic inflammatory conditions.

In the anterior lobe of the pituitary gland (AP), non-endocrine cells regulate hormone secretion by endocrine cells. However, the functions of non-endocrine cells in the AP during chronic pain are largely unclear. Here, we show that macrophages, but not folliculostellate (FS) cells, were selectively increased in the AP in the complete Freund's adjuvant (CFA)-induced chronic inflammatory pain model in rats. In addition, IL-1ß expression was increased in the AP, and the IL-1ß-immunopositive cells were identified as macrophages. On the other hand, increased macrophage density and IL-1ß expression were not detected in a neuropathic pain model induced by partial sciatic nerve ligation (PSL). Furthermore, we found c-Fos expression specifically in the somatotrophs under the chronic inflammatory pain condition. Because IL-1ß promotes growth hormone (GH) synthesis and release, our results suggest that AP macrophage contributes to GH release through IL-1ßduring chronic inflammatory pain.　.

Intracerebroventricular fluvoxamine administration inhibited pain behavior but increased Fos expression in affective pain pathways.

Anti-nociceptive effects of fluvoxamine, administered by intracerebroventricular (i.c.v.) injection, include inhibited pain behavior in both formalin-induced acute pain (p<0.05-0.01) and sciatic nerve ligation-allodynia (p<0.03). A 5-HT1 receptor antagonist (WAY-100635) and a 5-HT2 receptor antagonist (ketanserin), injected i.c.v., induced hyperalgesia and inhibited fluvoxamine's anti-nociceptive effects. We also investigated how fluvoxamine affects neural activities in brain areas involved in affectional pain using Fos-like protein immunohistochemistry. The acute pain and allodynia increased Fos-positive cells in the prefrontal cortex (PFC), basolateral nucleus (BL) and central nucleus of the amygdala (Ce), indicating that these areas are involved in pain processing. Fluvoxamine did not block the Fos expression, though it did produce anti-nociception. Moreover, fluvoxamine alone increased Fos in the BL and PFC. Ketanserin did not decrease the Fos expression induced by fluvoxamine. The results indicated that 5-HT2 receptor activities participate minimally in Fos induction by fluvoxamine in the PFC and BL. In contrast, WAY-100635 affected the Fos expression produced by fluvoxamine. In the portion of the brain with affectional pain pathways, 5-HT1 receptor activities induced anti-nociceptive effects and decreased Fos expression with fluvoxamine, while 5-HT2 receptor activation affected to anti-nociceptive effects but did not induce Fos expression.

Intracerebroventricular injection of trazodone produces 5-HT receptor subtype mediated anti-nociception at the supraspinal and spinal levels.

Serotonin (5-HT) mediated anti-nociceptive effects induced by an anti-depressant, trazodone, are related to 5-HT(1A) receptor activities at the supraspinal level. 5-HT(3) receptor activation via the descending anti-nociceptive pathways may contribute to the trazodone mediated anti-nociception at the spinal level. Intracerebroventricular (i.c.v.) injection of trazodone dose-dependently impaired nociceptive responses in the formalin test in mice. Six and 15 microg of trazodone inhibited the early (P<0.05 or 0.01) and the late phases of the formalin test (P<0.05 or 0.01), while 3 microg had no effect. We examined the effects of a selective 5-HT(1A) receptor antagonist, WAY-100635, a single injection of which induced hyperalgesia (P<0.05), and blocked the anti-nociceptive effects of trazodone (P<0.01) when the two were simultaneously injected i.c.v. Intrathecal (i.t.) injection of a selective 5-HT(3) receptor antagonist, 3-tropanylindole-3-carboxylate hydrochloride, blocked the anti-nociceptive effects of i.c.v. trazodone (P<0.01), while WAY-100635 (i.t.) did not impair trazodone mediated anti-nociception. Trazodone mediated anti-nocicepton is related to serotonergic activity at both the supraspinal and the spinal level.

Mechanical stimulation activates small fiber mediated nociceptive responses in the nucleus gigantocellularis.

We characterized nociceptive discharges induced by mechanical stimulation and the modulating effects of orphanin FQ on noxious responses in the rat brain stem gigantocellular reticular nucleus (Gi). A pressure pulse of constant force and rising rate was delivered by a mechanical stimulator with feedback control, allowing responses to be analyzed statistically. A pressure pulse of 300 g, which evoked C-fiber mediated nerve responses, was delivered to the tail. Two excitatory (45/58) and one inhibitory (13/58) types of extracellular unit discharges were recorded in Gi. One of the excitatory types was a phasic discharge (13/45) elicited at the onset and/or the end of stimulation. Latencies of the phasic discharges (0.104+/-0.1 s) were shorter than those of other type (tonic) discharges (0.43+/-0.2 s). The tonic discharges (32/45), which frequently persisted past the end of stimulation without adaptation, were classified into two groups. The first group of tonic type units (23/45) was high threshold, like nociceptive specific neurons in the primary sensory cortex, while the second group of neurons (9/45) responded to a wide range of stimulus intensities. The mean frequency, response duration and spike numbers gradually increased with stimulus intensity change in all nine neurons. The neurons encode mechanical stimulus intensity with discharge frequency, response duration and evoked spike numbers. Local injection of orphanin FQ (200 ng/2 microl) changed high threshold tonic type spike numbers in a biphasic manner, i.e., there was an early phase suppression (5-30 min, p=0.016) and a late phase enhancement (30-60 min, p=0.027). In contrast, phasic type discharges did not show an altered discharge pattern in response to orphanin FQ. Thus, orphanin FQ affects small fiber-mediated nociceptive responses and may behave as a complex modulator of pain systems in the brain stem.