Identification of hub genes associated with COVID-19 and idiopathic pulmonary fibrosis by integrated bioinformatics analysis.

INTRODUCTION: The coronavirus disease 2019 (COVID-19), emerged in late 2019, was caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The risk factors for idiopathic pulmonary fibrosis (IPF) and COVID-19 are reported to be common. This study aimed to determine the potential role of differentially expressed genes (DEGs) common in IPF and COVID-19. MATERIALS AND METHODS: Based on GEO database, we obtained DEGs from one SARS-CoV-2 dataset and five IPF datasets. A series of enrichment analysis were performed to identify the function of upregulated and downregulated DEGs, respectively. Two plugins in Cytoscape, Cytohubba and MCODE, were utilized to identify hub genes after a protein-protein interaction (PPI) network. Finally, candidate drugs were predicted to target the upregulated DEGs. RESULTS: A total of 188 DEGs were found between COVID-19 and IPF, out of which 117 were upregulated and 71 were downregulated. The upregulated DEGs were involved in cytokine function, while downregulated DEGs were associated with extracellular matrix disassembly. Twenty-two hub genes were upregulated in COVID-19 and IPF, for which 155 candidate drugs were predicted (adj.P.value < 0.01). CONCLUSION: Identifying the hub genes aberrantly regulated in both COVID-19 and IPF may enable development of molecules, encoded by those genes, as therapeutic targets for preventing IPF progression and SARS-CoV-2 infections.

Suloctidil-induced hepatotoxicity.

Suloctidil is a new drug that is currently being evaluated in many clinical trials for use in dementia and thrombotic disorders. Hepatotoxicity has to date been reported exclusively in the European literature, and the few available histologic descriptions have been reported in the French language. We report a case of suloctidil-induced hepatotoxicity documented by serum liver biochemical tests and liver biopsy. Histologic features included focal necrosis of hepatocytes, mild hyperplasia of Kupffer cells, and other features suggestive of mild acute hepatitis.

Effect of suloctidil on tomographically quantitated platelet accumulation in Dacron aortic grafts.

Platelet deposition contributes to the thrombotic and embolic complications of prosthetic materials in man. To determine if the investigational platelet inhibitory drug suloctidil (200 mg 3 times daily) reduces platelet deposition on Dacron aortic grafts, a randomized, double-blind, crossover trial was conducted in 12 men with grafts that had been in place more than 9 months. Platelet deposition in the graft was assessed by quantitative analysis of planar images obtained at 24, 48 and 72 hours after injection of indium-111-labeled platelets. Also, a tomographic method of imaging and quantitating labeled platelet deposition in the graft was developed. Tomographic imaging was performed at 24 and 72 hours after platelet injection and was quantitated by a graft/blood ratio that compared indium-111 platelet activity in summed 1.8-cm-thick transaxial tomographic slices of the aortic graft to indium-111 platelet activity in well-counted whole blood. Compared with placebo, suloctidil failed to decrease the tomographic graft/blood ratio at 24 hours (6.2 +/- 1.3 vs 5.7 +/- 0.8) and 72 hours (11.4 +/- 2.9 vs 10.7 +/- 2.2). Similarly, the graft/blood ratio determined by planar imaging was not different between placebo and suloctidil therapy at 24 hours (1.7 +/- 0.3 vs 1.6 +/- 0.2), 48 hours (2.2 +/- 0.4 vs 2.4 +/- 0.4) or 72 hours (2.6 +/- 0.5 vs 2.8 +/- 0.5) after labeled platelet injection. Thus, suloctidil does not significantly reduce platelet deposition on chronically implanted Dacron grafts in humans.

[Superior protective activity of phenytoin against hypoxia in pharmacological screening test].

In the treatment of cerebral infarction, it is important to select drugs for inhibiting development of the pathology. In order to select markedly effective drugs among many drugs, it is possible to grasp the outline of drug effects by means of an experimental system with simplicity and regularity--a screening test. In the present study, we induced a hypoxic load by exposing mice to a gas mixture consisting of 4% O2 and 96% N2, and investigated the effects of various kinds of drugs with reference to the survival time(ST: mean +/- SE), the time until the respiratory arrest of the mice. In the control group (n = 110), ST was 170 +/- 6 sec, with a normal distribution, and no mice that survived for eight minutes or more after the load were found. In contrast, ST was 1,833 +/- 487 sec in the suloctidil-treated group (12.5 mg/kg, n = 11), 1,160 +/- 342 sec in the vitamin E group (200 mg/kg, n = 15), 602 +/- 74 sec in the pentobarbital group (50 mg/kg, n = 12) and 2667 +/- 452 sec in the phenytoin group (100 mg/kg, n = 10). On the other hand, no prolongation of ST was found in the groups to which vitamin C, coenzyme Q, cytochrome c, betamethasone, mannitol or germanium-132 were administered. The ratio of the mice that survived for one hour or more after the load was 0% in the control group, 45.5% in the suloctidil group (12.5 mg/kg), 23.5% in the vitamin E group (200 mg/kg), 0% in the pentobarbital group (50 mg/kg) and 70% in the phenytoin group (100 mg/kg).(ABSTRACT TRUNCATED AT 250 WORDS)

Measurement of reaction times in tasks of varying complexity: an indication of the degree and evolution of mental deterioration in the elderly.

In a group of 40 elderly patients with intellectual deterioration, slowing of behaviour was measured with an original reaction time apparatus. Three types of measurements in ascending degree of complexity were evaluated against each other. Intercorrelations, made with indicators of physical, mental and behavioural functioning, demonstrated that ascending complexity in reaction time measurements can be used as an evaluation of the degree of mental deterioration. An example of the use of the apparatus in the evaluation of the improvement after treatment with suloctidil is given.

An evaluation of suloctidil in the prevention of deep vein thrombosis in neurosurgical patients.

Suloctidil (200 mg t.i.d.) was compared with placebo in a randomized, double-blind trial to assess its value in preventing deep venous thrombosis (DVT) in high-risk neurosurgical patients, comprising 136 patients with brain or spinal tumour, head or spinal injury, or subarachnoid or intracranial hemorrhage. 125I fibrinogen leg scanning and impedance plethysmography were performed for up to 14 days to detect DVT. The two groups were also evenly balanced for DVT risk factors. Seventeen of 68 patients (25%) (95% confidence interval, 15-35%) treated with suloctidil and 12 of 68 patients (21%) (95% confidence interval, 11-32%) treated with placebo developed deep venous thrombosis. This observed difference in outcomes is not statistically significant (X2 = 1.096; p = 0.30). The estimated 95% confidence interval for the true difference in the incidence of DVT between suloctidil-treated and placebo-treated patients ranges from an 11% benefit in favour of suloctidil to an 18% benefit in favour of placebo. Major deep vein thrombosis occurred in two patients on suloctidil and three patients in the placebo group; there were no fatal pulmonary emboli during the 14-day study period, during which time four patients in each group died of non-thromboembolic complications. There was no observed difference in hemorrhagic complications. Long-term outcomes at three-months follow-up were similar between the two treatment groups. It is concluded that there is no real evidence that suloctidil (200 mg t.i.d.) is an effective regimen for the prevention of DVT in high-risk neurosurgical patients.

Studies of suloctidil in experimental thrombosis in baboons.

Suloctidil has been evaluated in the baboon for its antithrombotic efficacy using models of both acute and chronic arterial thrombogenesis. Acute thrombus formation was initiated by Dacron vascular grafts inserted as extension segments into chronic arteriovenous shunts. 111In-platelet deposition was measured by scintillation camera imaging for one hour. The results after oral administration of suloctidil (100 mg/kg/d in two divided doses) were not different from control studies. Moreover, concurrent heparin anticoagulation did not affect 111In-platelet deposition compared with control data. In contrast, ticlopidine (20 mg/kg/d) significantly decreased platelet deposition that was reduced further by the addition of heparin. Chronic arterial-thromboembolism was initiated by segments of polyurethane (Biomer) cannula introduced into chronic arteriovenous shunts. Thrombus formation by the polyurethane cannula was measured as 111In-platelet turnover (corrected for removal of senescent platelets). Cannula platelet consumption was unaffected by suloctidil (20 mg/kg/d given in two divided doses for two days preceding and throughout the period of platelet survival measurement). In contrast, dipyridamole (10 mg/kg/d) and sulfinpyrazone (100 mg/kg/d) completely interrupted cannula platelet consumption. We conclude that suloctidil probably has little or no effect on platelet-dependent thrombus formation.

A secondary prevention, randomized trial of suloctidil in patients with a recent history of thromboembolic stroke.

Four hundred and thirty-eight patients who had suffered a thromboembolic stroke not less than two weeks or more than four months previously, were entered into a placebo-controlled randomized clinical trial to determine whether suloctidil (200 mg t.i.d.) would influence the subsequent recurrence of stroke, the occurrence of myocardial infarction, or cardiovascular death. The two treatment groups were comparable at baseline with respect to important prognostic variables and there was good adherence to the study protocol during an average follow-up of 20 months. Significantly more patients complained of side-effects in the suloctidil group and more hepatotoxicity was also reported in the suloctidil group. Four cases of clinical hepatitis were suspected to be due to suloctidil, each of which was reversible on termination of study treatment; relative increases in SGOT and SGPT at three months in the suloctidil group were found to be mild and transient. The primary analysis of efficacy was based on the incidence of the first event of stroke, myocardial infarction or cardiovascular death, but excluding events that occurred more than 28 days after complete withdrawal from study medication for whatever reason. Thus, the primary analysis included 38 events in the suloctidil group and 47 in the placebo group (p = 0.17) representing a risk reduction of 24%. If total mortality is substituted for cardiovascular death, the corresponding figures are 47 in the suloctidil group and 58 in the placebo group (p = 0.08).(ABSTRACT TRUNCATED AT 250 WORDS)

Suloctidil en insuficiencia circulatoria cerebral / Suloctidil in cerebral circulatory insuficiency

Valoracion terapeutica del suloctidil sobre algunos signos y sintomas que forman parte del cuadro de insuficiencia circulatoria cerebral

Double-blind trial of suloctidil versus placebo in moderate to severe mental deterioration.

A double-blind, parallel group, placebo-controlled study was carried out in 30 elderly patients with moderate to severe mental deterioration to assess the effect of suloctidil on their mental condition. A battery of clinical and psychometric evaluations failed to demonstrate any significant differences between the two groups at the end of a 6-month treatment period during which patients received either 200 mg suloctidil or placebo 3-times daily. However, further analysis of the results showed that in the sub-group of patients with moderate mental deterioration on entry, suloctidil treatment produced significant improvement from baseline in the Rey 15 words test and the results were significantly different from those in patients with severe mental deterioration. No consistent changes were observed in the placebo group.

Suloctidil: long-term trial in the aged. Study of microcirculation, viscosity, red cell deformability, fibrinolysis and lipid fractions.

15 aged patients with clinical and laboratory evidence of cerebrovascular insufficiency and/or myocardial sclerosis were given suloctidil (Locton) at the daily dose of 200 mg X 3, for 180 days, under the conditions of an open trial. Blood and plasma viscosity, red cell deformability, total lipids, cholesterol, triglycerides, fibrinolysis (plasminogen, antiplasmin, euglobulins with and without activator, fibrinogen), and capillaroscopic parameters in the small conjunctival vessels (artery, vein, and capillary diameter, appearance of collaterals, red cell aggregation and flow homogeneity) were evaluated. After 30 days of treatment and particularly at the end of the trial a significant improvement of almost all these parameters was observed. Tolerance was always excellent.

Effect of suloctidil on platelet function in patients with shortened platelet survival time.

The effect of suloctidil (600 mg/day) on platelet survival time (PST) and plasma and urine betathromboglobulin (BTG) was studied in a double-blind, placebo-controlled six-week crossover trial in 13 patients with shortened PST (less than 110 hrs, exponential model). Mean PST after suloctidil (110.6 hrs) was significantly higher than in the placebo phase (94.5 hrs) (p = 0.04). Mean plasma BTG was significantly lower during the suloctidil phase (42.8 ng/ml) compared with the placebo phase (65.8 ng/ml) (p = 0.02), but there was no significant difference in urine BTG. These results suggest that suloctidil provides a platelet protective effect and therefore may be of benefit in reducing the frequency of platelet mediated thromboembolic events.

Hypocholesterolaemic activity of suloctidil: double-blind, crossover short-term and long-term treatment trial.

Two studies were carried out in patients with primary hyperlipidaemia to investigate the effect of suloctidil (200 mg 3-times daily) on serum cholesterol levels and other lipidaemic variables. The first study was a double-blind, crossover comparison of suloctidil and placebo in 23 patients. Patients were allocated at random to receive one or other treatment for 4 weeks, after a wash-out period of 4 weeks on placebo, and were then crossed over to the alternative medication for the following 4 weeks. Patients were kept on a controlled diet throughout the trial. In the second, long-term study, 28 patients were treated, after an initial washout period of 8 weeks on placebo, with suloctidil for periods of up to 1 year. As in the short-term trial, patients were maintained on a controlled diet. The results showed that suloctidil produced a statistically significant reduction in total serum cholesterol and serum triglycerides in the short-term and this reduction was maintained over the longer period of the second study. In addition, there was a concomitant and approximately proportional increase in HDL-cholesterol. Suloctidil was well tolerated and no serious side-effects were reported.