Systematic Review and Meta-Analysis Comparing the Safety of Natalizumab, Ocrelizumab, and Alemtuzumab in Treating Relapsing–Remitting, Primary Progressive, and Secondary Progressive Multiple Sclerosis

Three monoclonal antibodies—natalizumab (NTZ), ocrelizumab (OCR), and alemtuzumab (ALM)—are the mainstays for the treatment of both relapsing and progressive forms of multiple sclerosis (MS). Here, their safety in patients with MS is analyzed and compared for rational use, especially during the COVID-19 pandemic. All clinical studies published between 2016 and 2020 with the primary outcome of the occurrence of adverse events (AEs) with the use of NTZ, OCR, and ALM in the treatment of MS were systematically searched in the PubMed database. In this review, the percentage of patients reporting AEs was calculated and compared. The most common AEs associated with the use of NTZ, OCR, and ALM were infection and infestation. The percentage of patients reporting urinary tract infection, upper respiratory tract infection, and herpes was 16% using natalizumab, 7% using natalizumab and ocrelizumab, and 2% with ocrelizumab, respectively. The most common AEs, such as rashes, pyrexia, and influenza, were reported with ocrelizumab and alemtuzumab. Additionally, alemtuzumab was associated with immune thrombocytopenia (2%), respiratory infections (7%), and thyroid dysfunction (43%). All these data outcomes show that of the three monoclonal antibodies, natalizumab and ocrelizumab were associated with a reduced incidence of adverse events, making them a safer choice for MS.

Modulatory effect of dietary factors on iron-induced in vivo lipid peroxidation in liver and serum of albino rats.

Effect of a computed diet based on cereals and spices incorporated with either crude palm oil (CPO)/soybean oil (SBO)/cod liver oil (CLO) at 10% level in the diet in modulating iron-induced in vivo lipid peroxidation was carried out during a 12 week study in albino rats. Three groups of rats, each divided into three sets were fed diets based on casein/ragi/jowar incorporated with CPO or SBO or CLO. The casein group of rats did not receive any spice mixture, while the ragi and jowar groups received spice mixture at 2.5% level. Serum lipid analysis showed significant increase in cholesterol, LDL-c + VLDL-c and decrease in HDL-c levels in all the iron treated group of animals. In liver, non-significant increase in total cholesterol triglyceride and decrease in phospholipid levels were noted. Fatty acid profile of liver tissue exhibited low 18:2 levels in various experimental groups due to peroxidation of membrane lipids. Histopathological examination of liver tissue in particular showed mild cytoplasmic vacuolation in control group of rats fed ragi/jowar and moderate vacuolation in all the iron-treated groups. The results demonstrate that different dietary components can beneficially modulate free radical mediated oxidative stress induced by lipid peroxidation.

Effect of oxidative stress on serum and antioxidant enzymes in liver and kidney of rats and their modulation through dietary factors.

Modulatory effect of a formulated diet based on cereals, pulses and spices incorporated with crude palm oil (CPO), soybean oil (SBO) or cod liver oil (CLO) at 10% dietary level on oxidative stress and antioxidant enzymes was studied in liver and kidney tissues. Activity of alkaline phosphatase (ALP) and acid phosphatase (ACP) increased significantly in serum in various experimental groups. Significant increase in hepatic antioxidant enzymes, catalase, glutathione peroxidase (GPx) was also seen in the experimental groups. SOD activity showed a mixed response. Further, kidney antioxidant enzymes did not show much change compared to those in liver. The results indicated dietary lipid as the key players in determining cellular susceptibility to oxidative stress, which could be modulated by cereals, pulses and spices in the diet.

Long-term feeding effect of thermally oxidised oils on antioxidant enzymes in rats.

Long term feeding effect of thermally oxidised oils on activities of hepatic antioxidant enzymes viz. catalase, glutathione peroxidase (GPX), glutathione-S-transferase (GST) and superoxide dismutase (SOD) at 5 and 20% level for 20 weeks was studied in laboratory rats. Activity of catalase increased in heated and fried oil fed group of rats, whereas activities of GPX, GST and SOD decreased in both heated and fried oil groups. Increase or decrease in activities of these enzymes may be related to several factors like heating and frying conditions, nature of fat, extent of peroxidation, presence of antioxidants, duration of feeding, beside other factors.

Absence of in vivo mutagenic potency of heated and fried oils in mice.

The mutagenic potency of heated and fried oils (under laboratory conditions), viz. peanut, sesame and coconut oils were studied employing two well validated in vivo mammalian assays, viz. bone marrow micronucleus assay and the sperm morphology assay in albino mice. In the bone marrow micronucleus assay oral doses of fresh, heated and fried oils (7.5 ml and 30.0 ml/kg body weight) did not induce any increase in the incidence of micronucleated polychromatic erythrocytes. Intragastric administration of oils at the highest dose (30.0 ml/kg body weight/day) for 5 consecutive days in male mice did not produce any morphological effect either on the testicular or epididymal weights and histology. No significant alterations were observed in the caudal sperm counts at any of the sampling intervals and also there was no treatment related increase in the incidence of sperm head abnormalities. It is concluded that controlled thermal treatment as well frying of these oils did not produce appreciable amount of mutagens which could be detected under in vivo situations.

gamma-Glutamyl transpeptidase activity in mice: age dependent changes and effect of cortisol.

gamma-Glutamyl transpeptidase (gamma-GT) activity in various organs of mice during ontogenesis has been determined. The activity profile in foetus, neonates and the adult animal were compared to ascertain the functional significance of the enzyme. In addition, the effect of cortisol on gamma-GT activity in adult kidney is presented.

Lipid profile of cultured cells of apple (Malus sylvestris) and apple tissue.

The potentiality of apple cell cultures to synthesize not only higher quantities of lipids than apple fruit but also different classes of lipids is noted. Total lipid was 15-fold higher in apple callus than in the original tissue. On callusing, linoleic acid decreased from 66% to 14%, while linolenic acid showed a very large increase from 0·9% to 44%. Stearic and oleic acids also increased in callus. The relative amounts of sterol/hydrocarbon and diglyceride fractions were higher in callus cultures, while apple tissue showed higher levels of triglycerides and sterol. Phosphatidylethanolamine and phosphatidylglycerol seemed to be newly synthesized during callusing while other phospholipids such as lysophosphatidylcholine, lysophosphatidylethanolamine, phosphatidylinositol and phosphatidic acid decreased. There was much higher glycolipid in apple callus than in the original tissue. The ratio of neutral lipid to polar lipid was higher in apple than in apple callus.