COVID-19 Induces Neuroinflammation and Suppresses Peroxisomes in the Brain.

OBJECTIVE: Peroxisome injury occurs in the central nervous system (CNS) during multiple virus infections that result in neurological disabilities. We investigated host neuroimmune responses and peroxisome biogenesis factors during severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection using a multiplatform strategy. METHODS: Brain tissues from coronavirus disease 2019 (COVID-19) (n = 12) and other disease control (ODC) (n = 12) patients, as well as primary human neural cells and Syrian hamsters, infected with a clinical variant of SARS-CoV-2, were investigated by droplet digital polymerase chain reaction (ddPCR), quantitative reverse transcriptase PCR (RT-qPCR), and immunodetection methods. RESULTS: SARS-CoV-2 RNA was detected in the CNS of 4 patients with COVID-19 with viral protein (NSP3 and spike) immunodetection in the brainstem. Olfactory bulb, brainstem, and cerebrum from patients with COVID-19 showed induction of pro-inflammatory transcripts (IL8, IL18, CXCL10, NOD2) and cytokines (GM-CSF and IL-18) compared to CNS tissues from ODC patients (p < 0.05). Peroxisome biogenesis factor transcripts (PEX3, PEX5L, PEX11ß, and PEX14) and proteins (PEX3, PEX14, PMP70) were suppressed in the CNS of COVID-19 compared to ODC patients (p < 0.05). SARS-CoV-2 infection of hamsters revealed viral RNA detection in the olfactory bulb at days 4 and 7 post-infection while inflammatory gene expression was upregulated in the cerebrum of infected animals by day 14 post-infection (p < 0.05). Pex3 transcript levels together with catalase and PMP70 immunoreactivity were suppressed in the cerebrum of SARS-CoV-2 infected animals (p < 0.05). INTERPRETATION: COVID-19 induced sustained neuroinflammatory responses with peroxisome biogenesis factor suppression despite limited brainstem SARS-CoV-2 neurotropism in humans. These observations offer insights into developing biomarkers and therapies, while also implicating persistent peroxisome dysfunction as a contributor to the neurological post-acute sequelae of COVID-19. ANN NEUROL 2023;94:531-546.

Dengue virus identification by transmission electron microscopy and molecular methods in fatal dengue hemorrhagic fever.

Dengue virus is the most significant virus transmitted by arthropods worldwide and may cause a potentially fatal systemic disease named dengue hemorrhagic fever. In this work, dengue virus serotype 4 was detected in the tissues of one fatal dengue hemorrhagic fever case using electron immunomicroscopy and molecular methods. This is the first report of dengue virus polypeptides findings by electron immunomicroscopy in human samples. In addition, not-previously-documented virus-like particles visualized in spleen, hepatic, brain, and pulmonary tissues from a dengue case are discussed.

Expression patterns of ornithine decarboxylase and c-met in growing Yoshida AH-130 hepatoma.

The expression of the two proto-oncogenes ornithine decarboxylase and c-met was examined during various phases of growth of Yoshida AH-130 ascites hepatoma. Ornithine decarboxylase (ODC) and c-met mRNA levels declined progressively from day 5 (exponential growth-phase) until day 14 (quasi-stationary growth-phase). Transcription rate for both the genes remained constant between days 5 and 10, while decreasing at day 14. ODC activity was consistent with ODC mRNA level during hepatoma growth. In host liver, ODC mRNA accumulated 5 and 14 days after tumor transplantation, while c-met mRNA level was elevated until day 10 and diminished at day 14. ODC activity triplicated at day 14 in host liver. The progressive decline in the expression of ODC and c-met observed in hepatoma might be one of the mechanisms important for the control of tumor growth.

Central dopaminergic function in anorexia and bulimia nervosa: a psychoneuroendocrine approach.

Data on central dopamine (DA) function in patients with Anorexia Nervosa (AN) and Bulimia Nervosa (BN) are contradictory. To tentatively clarify the brain secretory state of the amine and its relationship with the nutritional impairments and/or the psychopathological aspects of the two disorders, we measured the responses of growth hormone (GH) to acute stimulation with apomorphine (APO), a selective D-1 and D-2 receptor agonist, in 16 AN patients, 8 restricted (AN-R) and 8 bingeing-purging (AN-BP), in 7 BN patients and in 8 healthy controls (CTR). Interference of impairment of the somatotropic axis in the GH response to APO stimulation was excluded by measuring the GH and insulin-like growth factor-1 (IGF-1) basal levels and GH responses to growth hormone-releasing hormone (GHRH) stimulation. Psychological aspects of patients and controls were investigated by the rating scales Eating Disorder Inventory (E.D.I.), Bulimic Investigation Test Edinburgh (B.I.T.E)., and Yale-Brown Cornell Eating Disorder Scale (YBC-ED). Basal GH levels were significantly higher and those of IGF-1 lower in AN-R than in AN-BP, BN and CTR subjects. GH responses to GHRH stimulation were significantly higher in AN-R than in AN-BP and BN patients and in CTR. GH responses to APO stimulation were significantly lower in AN-R and AN-BP than in BN and CTR subjects, suggesting that at the hypothalamic level there is a subsensitivity of postsynaptic D-2 receptors and possibly a presynaptic DA hypersecretion. The altered GH responses to APO stimulation did not correlate with the Body Mass Index, while they correlated negatively with E.D.I. scores.

Transcranial Doppler sonography in fulminant hepatic failure.

UNLABELLED: The clinical course of patients with fulminant hepatic failure (FHF) is often worsened by the presence of cerebral edema and endocranial hypertension. In spite of the multiple studies using Transcranial Doppler Sonography (TCDS), few have shown the cerebral blood flow (CBF) pattern among patients with encephalopathy resulting from FHF. OBJECTIVE: Our objective was to characterize the CBF pattern in these patients through the use of TCDS to provide therapeutic strategies. METHOD: The TCDS pattern was assessed in five patients diagnosed with FHF and compared with a control group who displayed critical neurologic conditions not associated with FHF. Pulsatile index, systolic, diastolic, and mean velocity of the middle cerebral artery were measured. RESULTS: The mean age of patients with FHF was 45.4 years. One hundred percent were women, with viral hepatitis as the predominant etiology. A cerebral hypoperfusion pattern was found in 80% of the FHF group and 40% of the control group. In the former group there was no evidence of hyperemia, as there was among 20% of the control group. The mean values of velocity and pulsatile index were 36.6 cm/sec and 2.4, respectively, in the FHF group and 47.8 cm/s and 1.8 in the control group (P=0.268, P=0.402). CONCLUSIONS: FHF patients show a predominance of cerebral hypoperfusion pattern with mean velocities lower than normal values and an increased pulsatile index. We recommend that clinicians take appropriate measures to improve cerebral perfusion and avoid hypoxia. Hyperventilation as a first level measure is contraindicated.

Synthesis and antimicrobial properties of cephalosporin derivatives substituted on the C(7) nitrogen with arylmethyloxyimino or arylmethyloxyamino alkanoyl groups.

Some 7-aminocephalosporanic acid (7-ACA) derivatives substituted on the C(7) nitrogen with 2-(arylmethyloxyimino)propionyl (3a-f), 2-(arylmethyloxyamino)propionyl (4a-d) and (arylmethyloxyamino)acetyl (2a-d) moieties were synthesized by reaction of the appropriate acylating agents with 7-ACA protected as a t-butyl ester, followed by removal of the t-butyl protecting group. The new compounds, tested in vitro for their antimicrobial activity against Gram-positive and Gram-negative bacteria, proved to possess a modest activity directed only against Gram-positive microorganisms.

Synthesis and antimicrobial activity of benzo[a]dihydrocarbazole and benzotetrahydrocyclohept[1,2-b]indole derivatives.

A certain number of benzodihydrocarbazoles and benzotetrahydrocycloheptindoles were synthesized and tested for their antimicrobial activity. Compounds substituted on the nitrogen of the tetracyclic systems with a dimethylaminopropyl chain showed an antibacterial activity directed almost exclusively towards Gram-positive bacteria, while their N-unsubstituted analogs were completely inactive.

Monoclonal antibody to dengue capsid protein: its application in dengue studies.

Dengue fever (DF) and dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS) are considered the most important arthropod-borne viral diseases in terms of morbidity and mortality. The emergency and severity of dengue (Den) infections increase the necessity of an early, quick and effective dengue laboratory diagnostic. Viral isolation is considered a gold standard for diagnosis of dengue infection using monoclonal antibodies (mAbs) as a tool for determining serotype specificity. Alternatives have been used to improve sensitivity and time to dengue diagnosis. Based on the early expression of dengue C protein in the life cycle, we focused our study on the application of an anti-dengue 2 virus capsid protein mAb in dengue diagnosis. The kinetic expression of dengue-2 capsid in mosquito cells and its immuno-localization in experimentally infected suckling albin Swiss (OF-1) mice brain tissues was established. The results demonstrate the possible utility of this mAb in early dengue diagnosis versus traditional isolation. In addition, a preliminary study of an enzyme immunoassay method using 8H8 mAb for specific detection of dengue C protein antigen was performed, making possible recombinant C protein quantification. The results suggest that detection of dengue capsid protein could be useful in the diagnosis of early dengue infection.

Neurotransmitter and hormonal background of hostility in anorexia nervosa.

Marked hostility toward relatives, therapists and friends is very frequently observed in anorexia nervosa (AN) as expression of outward-directed aggressiveness which interferes with the therapeutic programs of the patients. With the purpose to investigate this aspect of the disorder and its biological background, we studied in anorexics some neurotransmitter-hormonal secretions which are known to modulate aggressivity-hostility by measuring plasma concentrations of total (TT) and free testosterone (FT), total estrogens (TE), the TT/E and FT/TE ratios, and the serotonergic function by measuring basal prolactin (PRL) levels and responses to stimulation with the specific serotonin (5-HT)-releasing agent D-fenfluramine (D-Fen). In 13 women with AN, 5 of the restricted (AN-R) and 8 of the bingeing/purging type (AN-BP) in an active phase of the disease, and in 13 healthy controls matched for sex and age, we measured hostility by the SCL-90 scale (subscale items 11, 24, 63, 67, 74, 81). Basal TT, FT, TE, TT/TE, FT/TE, PRL values and PRL responses to D-Fen and to saline administration were measured radioimmunologically in AN patients and controls. Hostility was significantly higher in AN patients than in controls, TT, FT and TE concentrations were significantly lower in AN patients than in controls, TT/TE ratio was significantly higher in AN patients than in controls, and FT/TE ratio was not different in the two groups. In AN patients and controls, hostility correlated positively with TT and FT values. Basal PRL values and responses to D-Fen administration were significantly lower in anorexics than in controls, but they did not correlate with the degree of hostility in either patients or controls. In conclusion, hostility is higher than normal in anorexics, and its severity seems to be linked to the secretion of FT and not to the alterations in the 5-HT function.

Traumatismo de carótida primitiva. Solución quirúrgica con clampaje total sin déficit neurológico / Common carotid injury. Surgical solution with total clampage without neruologic deficit

Presentamos el caso de un paciente masculino de 8 años de edad, que luego de un traumatismo en la región lateral izquierda del cuello, por caída y penetración de cuerpo extraño (astilla de madera) que permanece durante 18 días entre el músculo esternocleidomastoideo y la arteria carótida primitiva izquierda a quien penetraba doblemente por sus caras laterales, mostró en el momento de la exploración, lesión anfractuosa de dicha arteria; que obligó a un clampaje distal y proximal, resección de un centímetro de arteria contusionada con lesión de sus tres capas y anastomosis termino – terminal a puntos separados con polipropileno 5 x 0. Una adecuada protección cerebral fue orientada y cumplida entre anestesistas y cirujanos vasculares durante el transoperatorio como la posición del paciente, hipotermia, furosemida, manitol, betnazol, y bicarbonato. Medidas que unida a la revascularización garantizaron una recuperación optima del paciente sin déficit neurológico (AU)

We presented/displayed the case of a masculine patient of 8 years of age, which after a traumatism in the left lateral region of the neck, by fall and penetration of strange body (wood chip) that remains during 18 days between the esternocleidomastoideo muscle and the artery left primitive carotid to that penetrated doubly by its lateral faces, showed at the moment of the exploration, rough injury of this artery; that it forced a distal and proximal clampage, resection of a centimeter of artery contusionada with injury of its three layers and anastomosis I finish terminal to separated points with polypropylene 5 xs 0. A suitable cerebral protection was oriented and fulfilled between anesthetists and surgeons you will tilt during operation like the position of the patient, hypotherm, furosemida, manitol, betnazol, and bicarbonate. Measures that together with the revascularización guaranteed an optimal recovery of the patient without neurological deficit (AU)

Comportameinto de la disección aórtica / Evolution of aortic dissection

Las manifestaciones clínicas de la disección aórtica aguda dependen de las variaciones del flujo sanguíneo en el canal sanguíneo y la extensión de la oclusión periférica o central de la arteria. Se realizó un estudio descriptivo transversal empleando como universo a todos los pacientes egresados con el diagnóstico de disección aórtica del Hospital Provincial “Saturnino Lora” de Santiago de Cuba en el periodo de enero del 2000 a octubre del 2005 con el objetivo de conocer el comportamiento de esta entidad hallando como resultado que la disección aórtica predominó en pacientes de 58 años, del sexo masculino y la raza negra ; la estadía promedio para esta enfermedad fue de 21 días, el antecedente personal de hipertensión arterial fue encontrado en un gran porcentaje de los casos; los síntomas y signos predominantes fueron el dolor torácico, y los propios de la hipertensión arterial y la insuficiencia aórtica, los métodos diagnósticos mas empleados fueron el ecocardiograma transtorácico, el ultrasonido abdominal, la aortografía y la tomografía axial computarizada, las disecciones aórticas más frecuentes fueron agudas y los tipo I y II que comienzan en la aorta ascendente (AU)

The clinical manifestations of the acute aortic dissection depend on the variations of the sanguineous flow in the sanguineous channel and the extension of the peripheral or central occlusion of the artery. A cross-sectional descriptive study was made using like universe to all the patients withdrawn with the diagnosis of aortic dissection of Dark-brown the Provincial Hospital “ Saturnine ” of Santiago of Cuba in the period of January of the 2000 to October of the 2005 with the objective to know the behavior this organization finding like result that the aortic dissection predominated in patients of 58 years, masculine sex and the black race; the average for this disease was of 21 days, the personal antecedent of arterial hypertension was found in a great percentage of the cases; the predominant symptoms and signs were the thoracic pain, and own of the arterial hypertension and the aortic insufficiency, the methods diagnoses but used were transesophageal echocardiography, the abdominal ultrasound, the aortography and the computed tomography, the more frequent aortic dissections were acute and the type I and II that begins in the ascending aorta (AU)