Possible mechanisms of diabetic fetopathy

By using immunoaffine chromatography and ELISA it was found that 30-35% polyclonal of anti-insulin antibodies (AB1) in sera of diabetes patients has bound with high-affinity to Nerve Growth Factor (NGF). This indicates the presence of common epitop(s) in both molecules and could be a reason for NGF deprivation during formation of the nervous system in fetuses of diabetic pregnant women. Patient sera also usually characterized by elevated level of antiidiotypic antibodies (AIAb2) which interact with membrane insulin receptors, and may induce the general metabolic disturbances in fetus and newborns from diabetic mothers, fatal sometimes. High levels of anti-insulin/NGF Ab1 may bind excess of AIAb2 and prevents the insulin receptors dysfunction (typical for newborns in satisfactory health state). On the other hand--children with elevated levels of Ab1 at age 1-3 years often revealed clinical signs of neuropathology.     

Possible mechanisms of TSH--independent thyroid growth

Considerable evidence has been accumulated which indicates the participation of the autonomic nervous system in the growth of adrenals, ovaries, testes and thyroid lobes. Results have been gathered indicating that the pituitary is not required for the growth of the thyroid, adrenals and ovaries; interest is currently focused on the involvement of the pineal gland in the control of growth not only of the gonads, but also of the thyroid. This paper summarizes the data currently available on the concepts of thyroid hypertrophic and hyperplastic mechanisms, which occur independently of thyrotropin (TSH), and which suggest the existence of a reciprocal relationship between the pineal and the thyroid.     

Possible mechanisms of the death of cardiomyocytes

Current concepts on the mechanisms of cardiomyocyte (CMC) alteration and death are reviewed basing on the author's and literature data. Degradation of the adenine nucleotide pool plays a principal role in the reversible damage and death of the CMC. The transition of the reversible changes into the irreversible ones is determined by the formation of structural defects in the plasmalemma. Ultrastructural alterative changes are somewhat specific with regard to the agent that caused the cell death. The following ultrastructural types of the CMC degeneration and death are distinguished: 1) primary ischemic type of the cell degeneration and death; 2) secondary calcium degeneration and death; 3) primary rigor type of calcium degeneration and death; 4) primary lytic type of calcium degeneration and death; 5) vacuolar type of calcium degeneration and death; 6) hypoxic variant of the primary rigor type of calcium degeneration and death; 7) hypoxic variant of the primary lytic type of calcium degeneration and death.     

Possible mechanisms of synapse formation in ontogeny

Neuroscience and Behavioral Physiology -     

Possible induction of food allergy during mite immunotherapy

Sera of 17 patients receiving immunotherapy for house-dust mite allergy were tested for IgE antibodies against snail and shrimp. Serum samples were taken at the start of immunotherapy and 14—20 months later. While the average IgE response to mite, Der p 1, and Der p 2 did not alter significantly, the average response to snail showed a significant increase. This included two conversions from negative to strongly positive. These novel IgE antibodies against snail were shown to be cross-reactive with mite. Three patients had a positive RAST for shrimp. For one of them, a strong increase of IgE against shrimp (and snail) was observed. In 2/3 snail/shrimp-positive sera, IgE antibodies against the cross-reactive allergen tropomyosin from mite, snail, and shrimp were demonstrated. A clear IgE response to snail (> 10% binding in a snail RAST) was confirmed by a positive skin prick test (SPT) for 6/10 patients. The two patients with antitropomyosin IgE also had a positive SPT for shrimp, and demonstrated the oral allergy syndrome (OAS) after eating shrimp. The observations in this study indicate that house-dust mite immunotherapy is accompanied by the induction of IgE against foods, including tropomyosin-reactive IgE. Food allergy (OAS) was observed in patients that had IgE antibodies against this cross-reactive allergen. In conclusion, induction of IgE during mite immunotherapy might occasionally cause allergy to foods of invertebrate animal origin.     

胆囊收缩素促坐骨神经再生的可能机制

背景：前期实验发现,八肽胆囊收缩素能促进大鼠坐骨神经损伤后的再生,但具体机制仍不清楚。目的：筛选有效指标,尝试从神经生长因子及神经再生微环境的角度分析八肽胆囊收缩素促进大鼠坐骨神经再生的机制。方法：选择健康SD大鼠,制备坐骨神经单侧离断伤模型后随机分为2组,八肽胆囊收缩素治疗组造模后连续7 d腹腔注射八肽胆囊收缩素8 nmol/kg,对照组腹腔注射等量生理盐水。检测两组大鼠局部神经生长因子蛋白表达、脊髓诱导型一氧化氮合酶水平、血清超氧化物歧化酶活性和丙二醛浓度,同时检测脊髓凋亡细胞数。结果与结论：八肽胆囊收缩素治疗组大鼠局部神经生长因子蛋白表达高于对照组(P < 0.01),脊髓诱导型一氧化氮合酶和凋亡细胞数低于对照组(P < 0.01),血清超氧化物歧化酶活性高于对照组且丙二醛浓度低于对照组(P < 0.01,0.05)。说明胆囊收缩素促进坐骨神经再生的可能机制包括保护神经元、抗细胞凋亡、抑制炎性反应、抗NO及氧化反应、抗丙二醛减轻自由基损伤等方面外,还可刺激神经生长因子的表达和释放。 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程全文链接：     

Possible mechanisms of cholesterol elevation aggravating COVID-19

Importance: Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs.Observations: Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In in vitro studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable.Conclusions and Relevance: Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.     

Possible mechanisms of allergic reactions of the skeletal muscle

The effects of denervation and sensitization alone and in combination on the isometric contractions of guinea pig diaphragmal muscle are studiedin vitro. Denervated diaphragmal muscle contracts in response to histamine, the reaction being abolished by the histamine receptor blocker dimedrol. After sensitization, these muscles respond to histamine and specific antigen, contraction being prevented by incubation with dimedrol and the mast cell blocker Intal. The possible mechanisms of reactions in the muscles are discussed. Translated fromByulleten' Ekskerimental'noi Biologii i Meditsiny, Vol. 122, No. 11, pp. 547–550, November, 1996     

Possible mechanisms of delay in initiation of voluntary movements

Studies were made of psychomotor responses and accompanying cortical evoked potentials in healthy subjects and patients with Parkinson’s disease. Measurements showed that delays in a variety of psychomotor responses resulted from delays in movement initiation. The frontal regions showed increases in the N2 component of evoked potentials and delayed development of P3 waves. It is suggested that delayed initiation of movements in patients with Parkinson’s disease might be associated with strengthening of frontal inhibitory systems, preventing the onset of movements. Laboratory for the Physiology of Higher Nervous Activity, I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, 6 Makarov Bank, 199034 St. Petersburg, Russia. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 83, No. 1-2, pp. 109–116, January–February, 1997.     

Possible molecular mechanisms of brain dysfunction in phenylketonuria]

Recent experimental data are summarized about changes in the functioning of calcium ion channels in clonal cellular lines (pheochromocytoma PC12) and hippocampal neurons of newborn rats on the background of altered intracellular level of aromatic amino acid L-tyrosine or its precursors L-phenylalanine. Elevation of the level of L-phenylalanine persistently down-regulated the high-threshold voltage-operated calcium channels in both types of cells without affecting the low-threshold ones in hippocampal neurons. This depression could be to some extent reversed by elevation of the level of L-tyrosine. Thus both amino acids seem to exert a long-lasting antagonistic modulatory effect on the corresponding channels, mediated probably through changes in tyrosylation of some cytoskeletal proteins. The participation of these molecular mechanisms in brain dysfunction during congenital disease phenylketonuria is suggested.     

The psychobiology of hostility: Possible endogenous opioid mechanisms

This study examined the role of endogenous opioids in the relation between hostility and cardiovascular stress responsiveness. Forty-six men completed the Cook-Medley Hostility Scale and experienced a laboratory pain stressor once under opioid blockade and once under placebo. Hostility scores were significantly related to the magnitude of change in cardiovascular reactivity/recovery resulting from opioid blockade. Low scorers on the Cynicism subscale displayed increases in heart rate (HR) reactivity under blockade relative to placebo, with reactivity decreases noted in high scorers. Low Hostile Affect scores were similarly associated with impaired diastolic blood pressure recovery under opioid blockade. HR recovery results were somewhat different, with high scorers on Aggressive Responding and the total Cook-Medley displaying improved HR recovery under opioid blockade, with no change noted in low scorers. These data provide preliminary support for the hypothesis that low hostile individuals rely on endogenous opioids for buffering cardiovascular stress responsiveness, but high hostiles do not.     

Possible supplemental mechanisms in the pathogenesis of AIDS.

Multiple and diverse mechanisms have been proposed as supplements to the HIV-1 virus in the destruction of CD4+ cells and the pathogenesis of AIDS. But it is now realized that 100 times more CD4+ cells are infected with HIV-1 than was originally thought to be the case, and many antigen-presenting cells are infected as well. In addition to the direct cytopathic effect of the virus, one or a few supplemental mechanisms may well suffice to explain the progressive loss of CD4+ cells, e.g., the considerable variation in the virus and/or the destruction of uninfected CD4+ cells by one immunological mechanism or another. However, it is not yet possible to state confidently which additional mechanism(s) is important. Identification of the nature of this supplemental process has become essential for successful, nonharmful intervention.     

Lectin-dependent neutrophil-mediated cytotoxicity. II. Possible mechanisms.

The mechanisms whereby neutrophils become cytotoxic to chicken erythrocyte (CRBC) target cells were investigated in a system of lectin-dependent neutrophil-mediated cytotoxicity (LDNMC). Through the use of drugs and specific metabolic inhibitors, LDNMC was found to be dependent on energy supplied by anaerobic glycolysis and on other active metabolic functions of the neutrophil. 2-Iodoacetamide, 2-deoxy-D-glucose, di-isopropyl-fluorophosphate, colchicine, cytochalasin B, and dibutyryl cyclic AMP all caused dose-dependent inhibition of cytotoxicity, while inhibitors of protein and nucleic acid synthesis were without effect. Cell surface membrane-active agents, such as chloroquine, hydrocortisone and chlorpromazine inhibited cytotoxicity, while vitamin A caused enhancement. Lectins which agglutinated neutrophils, but not necessarily CRBC, such as phytohaemagglutinin (PHA-P), concanavalin A (Con A), soybean agglutinin (SBA), and Ricinus communis agglutinin (RCA), mediated cytotoxicity while lectins which did not cause agglutination, such as pokeweed mitogen (PWM), did not mediate cytotoxicity. Preincubation of neutrophils, but not CRBC with PHA-P, resulted in time-dependent enhancement of cytotoxicity, while pre-incubation with Con A yielded progressive inhibition of cytotoxicity. These studies suggest that lectin binding to the cell surface causes alterations of the membrane, that LDNMC requires cell to cell surface contact, and that cytotoxicity depends on active metabolic processes.