Ductus Arteriosus, Patent ; therapy ; Humans ; Infant, Newborn ; Infant, Premature

Objective To study the effects of moderate hypothermia on cerebral glucose and ATP contents andmitochondrial succinate dehydrogenase (SDH) activity in neonatal rats with hypoxic-ischimic brain damage (HIBD).Methods Seven-day-old Sprague-Dawley rat pups were subjected to ligation of the left carotid artery followed by exposureto hypoxia environment of 8 % O2 for 2 h, then they were randomly assigned into normothermic recovered group ( Ingroup) and moderate-hypothermic recovered group (IH group). The sham-operated rats which were used as the controlwere assigned into the normothermic control group (NC group) and moderate-hypothermic control group (HC group).The contents of glucose and ATP and activity of mitochondrial SDH were assayed at 0, 2, 6, 24, 48, 72 h after HIBD.Results The cerebal glucose contents in the IN and IH groups were significantly lower than those of the NC and Hcgroups 0 h after HIBD. Two hours after HIBD, the glucose content recovered to norhal level. The concentration of ATPand activity of SDH in the IN group decreased first, then they recovered gradually and reached a peak 72 hours afterHIBD. After 6 hours or 2 hours of HIBD, the ATP content or SDH activity of the brain in the IH group weresignificantly higher than those in the IN group. The ATP concentration was closely related to the SDH activity ( r =0.515, P ＜0.01). Conclusions Moderate hypothermia might protect brain tissue by inhibiting the decrease of SDHactivity and increasing the synthesis of ATP.

OBJECTIVETo investigate the protective effects of Huperzine A, a potent acetylcholinesterase inhibitor, against the hypoxic ischemic brain damage (HIBD) of the cognitive and morphology in the neonatal rats.

METHODSPostnatal 7 days old rats were given vehicle or Huperzine A (0.05 mg/kg or 0.1 mg/kg, i.p.) following HIBD (unilateral carotid artery ligation followed by hypoxia) or sham operation, and then tested the learning ability and memory in the Morris water maze (MWM) from 36 to 40 postnatal days. The performance in MWM (escape latency, probe time) were recorded to evaluate the learning and memory dysfunction. At the end of MWM trials, the rats were decapitated and their brains were histologically analyzed. The tissue loss in different brain regions including striatum, cortex, and hippocampus were analyzed by image analysis system. The CA(1) subfield neurons numbers were counted to evaluate the brain damage. The acetylcholinesterase histochemistry staining was used to determine the activity of acetylcholinesterase in different brain regions.

RESULTSCompared with sham-operated group, HIBD rats with the vehicle treatment displayed significant tissue losses in the hippocampus (including CA(1) neurons), cortex, and striatum, as well as severe spatial memory deficits (escape latency: 44 s vs 30 s, P < 0.05, probe time: 14 s vs 40 s, P < 0.01). Huperzine A treatment (0.1 mg/kg) resulted in significant protection against both HI-induced brain tissue losses and spatial memory impairments (mean escape latency: 34 s vs 44 s, P < 0.05, probe time: 35 s vs 14 s,P < 0.01). However, Huperzine A treatment (0.05 mg/kg) did not show any significant improvement of spatial memory impairments (mean escape latency: 45 s vs 44 s, P > 0.05, probe time: 17 s vs 14 s, P > 0.05), but moderate to severe brain tissue losses. There was a pronounced reduction of CA(1) neuron density in ipsilateral hemisphere of vehicle-treated group and 0.05 mg/kg Huperzine A group compared with contralateral hemisphere or ipsilateral hemisphere of sham-operated group and 0.1 mg/kg Huperzine A group (72 vs 232, P < 0.01, 72 vs 229, P < 0.01, respectively). There was a close linear correlation between the CA(1) neurons cell number and the mean escape latency for 5 d acquisition trials (r = 0.777, P < 0.01).

CONCLUSIONThe unilateral HI brain injury in a neonatal rat model was associated with cognitive deficits, and that Huperzine A treatment may be protective against both brain injury and spatial memory impairment. Huperzine A showed a therapeutic potential for the treatment of hypoxic-ischemic encephalopathy (HIE) caused by the perinatal asphyxia.

Acetylcholinesterase ; metabolism ; Alkaloids ; Animals ; Animals, Newborn ; Cerebral Cortex ; drug effects ; enzymology ; pathology ; Cognition Disorders ; drug therapy ; physiopathology ; Corpus Striatum ; drug effects ; enzymology ; pathology ; Female ; Hippocampus ; drug effects ; enzymology ; pathology ; Hypoxia-Ischemia, Brain ; drug therapy ; Male ; Maze Learning ; drug effects ; Neuroprotective Agents ; administration & dosage ; therapeutic use ; Rats ; Rats, Sprague-Dawley ; Sesquiterpenes ; administration & dosage ; therapeutic use ; Treatment Outcome

OBJECTIVETo investigate the effects of mild hypothermia on sequential events of neuronal apoptosis following hypoxic-ischemic brain damage (HIBD) in neonatal rats.

METHODSA model of HIBD was prepared by ligating the left common carotid artery in 7-day-old rats, followed by 8% hypoxia exposure. HIBD rats were randomly assigned into a hypothermia group (rectal temperature = 33 centi-degrees) and a normothermia group (rectal temperature = 36 centi-degrees). TUNEL, Haematoxylin and Eosin, and Nissl staining were used to detect neuronal apoptosis. Western blotting, RT-PCR and enzyme activity measurement were used to evaluate the changes of plasma and mitochondrial cytochrome c (Cyt c), caspase-3 mRNA expression and caspase-3 enzyme activity, respectively.

RESULTSThe number of apoptotic cells in the ipsilateral hemisphere of the hypothermia group was significantly reduced compared with that of the normothermia group at 72 hrs post-HI (6.4 +/- 1.7% vs 25.3 +/- 1.5%) (P < 0.01). Analysis of Western blotting showed that Cyt c levels increased in the cytosolic fraction, but decreased significantly in the mitochondrial fraction in the ipsilateral hemisphere of the hypothermia group at 24, 48 and 72 hrs of HI insult compared with the normothermia group (P < 0.05). Caspase-3 mRNA increased significantly after 24 hrs post-HI in the normothermia group, and this change became more pronounced with time. Mild hypothermia treatment decreased significantly caspase-3 mRNA expression at 24, 48 and 72 hrs post-HI (P < 0.05). Caspase-3 activity gradually increased 2 hrs after HI insult and peaked at 24 hrs in the normothermia group. Mild hypothermia treatment resulted in a significant reduction in caspase-3 activity in the ipsilateral hemisphere, with an optimal effect produced at 24 hrs post-HI (2.42 +/- 0.5 RFU vs 34.7 +/- 3.2 RFU; P < 0.01).

CONCLUSIONSMild hypothermia treatment attenuates neuronal apoptosis following HIBD, possibly through a reduction in Cyt c release from mitochondria and an inhibition of caspase-3 mRNA expression and its enzyme activity.

Animals ; Apoptosis ; Brain ; pathology ; Caspase 3 ; genetics ; metabolism ; Cytochromes c ; secretion ; Female ; Hypothermia, Induced ; Hypoxia-Ischemia, Brain ; pathology ; therapy ; Male ; RNA, Messenger ; analysis ; Rats ; Rats, Sprague-Dawley

Objective To investigate the effects of docosahexaenoic acid (DHA) on large-conductance Ca2 + -activated K+ ( BKCa ) channels and voltage-dependent K+ ( Kv ) channels in rat coronary artery smooth muscle cells ( CASMCs ),and evaluate the vasorelaxation mechanisms of DHA.Methods BKCa and Kv currents in individual CASMC were recorded by patch-clamp technique in whole-cell configuration.Effects of DHA at various concentrations (0,10,20,40,60 and 80 μ mol/L) on BKCa and Kv channels were observed.Results ( 1 ) DHA enhanced IBKCa and BKCa tail currents in a concentration-dependent manner while did not affect the stably activated curves of IBKCa+ IBKCa current densities were (68.2±22.8),(72.4 ±24.5),(120.4 ±37.9),(237.5 ±53.2),(323.6 ±74.8) and (370.6 ±88.2 )pA/pF respectively (P ＜ 0.05,n =30) with the addition of 0,10,20,40,60 and 80 μmol/L DHA concentration,and half-effect concentration ( EC50 ) of DHA was (36.22 ± 2.17 ) μmol/L.(2) IKv and Kv tail currents were gradually reduced,stably activated curves of IKv were shift to the right,and stably inactivated curves were shifted to the left in the presence of DHA.IKv current densities were (43.9 ±2.3),(43.8±2.3),(42.9±2.0),(32.3±1.9),(11.7±1.5) and (9.6 ±1.2)pA/pF respectively(P＜0.05,n =30) post treatment with 0,10,20,40,60 and 80 μmol/L DHA under manding potential equal to +50 mV,and EC50 of DHA was (44.19 ±0.63) μmol/L.Conclusion DHA can activate BKCa channels and block Kv channels in rat CASMCs,the combined effects on BKCa and Kv channels lead to the vasodilation effects of DHA on vascular smooth muscle cells.

Objective To investigate the effects of docosahexaenoic acid(DHA)on sodium channel current(INa)and transient outward potassium channel current(Ito)in rat ventricular myocytes and to evaluate potential anti-arrhythmic mechanisms of DHA.Methods INa and Ito of individual ventricular myocytes were recorded by patch-clamp technique in whole-cell configuration at room temperature.Effects of DHA at various concentrations(0,20,40,60,80,100 and 120 μmol/L)on INa and Ito were observed.Results (1) INa was blocked in a concentration-dependent manner by DHA,stably inactivated curves were shifted to the left,and recover time from inactivation was prolonged while stably activated curves were not affected by DHA.At-30 mV,INa was blocked to(1.51 ±1.32)%,(21.13±4.62)%,(51.61 ±5.73)%,(67.62 ±6.52)%,(73.49±7.59)%and(79.95±7.62)%in the presence of above DHA concentrations(all P<0.05,n=20),and half-effect concentration(EC50)of DHA on INa was(47.91±1.57)μmol/L(2) Ito were also blocked in a concentration-dependent manner by DHA,stably inactivated curves were shifted to the left,and recover time from inactivation was prolonged with increasing concentrations of DHA,and stably activated curves were not affected by DHA.At+70 mV,Ito was blocked to(2.61 ±0.26)%,(21.79±4.85)%,(63.11 ±6.57)%,(75.52 ±7.26)%,(81.82 ±7.63)%and(84.33±8.25)%,respectively,in the presence of above DHA concentrations(all P<0.05,n=20),and the EC50 of DHA on Ito was(49.11±2.68)μmol/1.Conclusion The blocking effects of DHA on APD and Ito may serve as one of the anti-arrhythmia mechanisms of DHA.

OBJECTIVETo investigate the clinical features and molecular diagnostic methods of three patients with DiGeorge anomaly.

METHODThe clinical manifestations and immunological features of the three cases with DiGeorge anomaly were analyzed. We detected the chromosome 22q11.2 gene deletion by fluorescence in situ hybridization (FISH).

RESULT(1) CLINICAL MANIFESTATIONS: All three cases had varying degrees of infection, congenital heart disease and small thymus by imaging; two cases had significant hypocalcemia (1.11 mmol/L and 1.22 mmol/L, respectively), accompanied by convulsions; only 1 case had cleft palate and all had no significant facial deformity. (2) Immunological characteristics: All three cases had varying degrees of T-cell immune function defects (percentage of T lymphocytes was 24% - 43%, absolute count was 309 - 803/µl), and levels of immunoglobulin G, A, M, and percent of B lymphocytes and absolute count were normal. (3) Detection of the chromosome 22q11.2 gene deletion: 400 cells of each case were detected. All cells showed two green and one red hybridization signal, indicating the presence of gene deletions in chromosome 22q11.2. (4) OUTCOME: All three cases were treated with thymosin, and appropriate clinical intervention for cardiac malformations, hypocalcemia, and were followed-up for 4 - 18 months, the prognosis was good.

CONCLUSIONDiGeorge anomaly showed diverse clinical manifestations. We should consider the disease if patients had congenital heart disease, thymic hypoplasia, hypocalcemia and/or impaired immune function. FISH for detecting chromosome 22q11.2 gene deletion can be used as accurate and rapid diagnostic method. Thymosin treatment and other clinical intervention may help to improve the prognosis of patients with partial DiGeorge anomaly.

Cells, Cultured ; Chromosome Deletion ; Chromosomes, Human, Pair 22 ; genetics ; DiGeorge Syndrome ; diagnosis ; genetics ; immunology ; Female ; Heart Defects, Congenital ; diagnosis ; genetics ; Humans ; Hypocalcemia ; diagnosis ; genetics ; In Situ Hybridization, Fluorescence ; Infant, Newborn ; Male ; T-Lymphocytes ; immunology ; Thymus Gland ; immunology ; pathology

The patient is a female infant, 4 months and 9 days old, who was admitted to the hospital due to recurrent fever, cough, and hepatomegaly for over a month. The patient was a healthy full-term infant with a normal birth history. At 2 months and 22 days after birth, she developed recurrent fever, cough, and respiratory distress. Chest imaging revealed diffuse bilateral lung lesions, and fiberoptic bronchoscopy showed interstitial changes in both lungs. These suggested the presence of interstitial lung disease. The patient also presented with hepatomegaly, anemia, hyperlipidemia, hypothyroidism, and malnutrition. Genetic testing indicated compound heterozygous variations in the MARS1 gene. This mutation can cause interstitial lung and liver disease, which is a severe rare disorder that typically manifests in infancy or early childhood. It is inherited in an autosomal recessive manner and characterized by early-onset respiratory insufficiency and liver disease in infants or young children. Since its first reported case in 2013, as of June 2023, only 38 related cases have been reported worldwide. This article reports the multidisciplinary diagnosis and treatment of interstitial lung and liver disease in an infant caused by MARS1 gene mutation.
Female ; Humans ; Infant ; Cough ; Hepatomegaly/pathology* ; Liver Diseases ; Lung/pathology* ; Lung Diseases, Interstitial/pathology* ; Mutation

Psoriasis is characterized by abnormal proliferation of keratinocytes, as well as infiltration of immune cells into the dermis and epidermis, causing itchy, scaly and erythematous plaques of skin. The understanding of this chronic inflammatory skin disease remains unclear and all available treatments have their limitations currently. Here, we showed that IMMH002, a novel orally active S1P modulator, desensitized peripheral pathogenic lymphocytes to egress signal from secondary lymphoid organs and thymus. Using different psoriasis animal models, we demonstrated that IMMH002 could significantly relieve skin damage as revealed by PASI score and pathological injure evaluation. Mechanistically, IMMH002 regulated CD3 T lymphocytes re-distribution by inducing lymphocytes' homing, thus decreased T lymphocytes allocation in the peripheral blood and skin but increased in the thymus. Our results suggest that the novel S1P agonist, IMMH002, exert extraordinary capacity to rapidly modulate T lymphocytes distribution, representing a promising drug candidate for psoriasis treatment.