A meta-analysis of ferric carboxymaltose versus other intravenous iron preparations for the management of iron deficiency anemia during pregnancy

Abstract Objective: We conducted a meta-analysis of randomized clinical trials evaluating the clinical effects of ferric carboxymaltose therapy compared to other intravenous iron in improving hemoglobin and serum ferritin in pregnant women. We also assessed the safety of ferric carboxymaltose vs. other intravenous iron. Data source: EMBASE, PubMed, and Web of Science were searched for trials related to ferric carboxymaltose in pregnant women, published between 2005 and 2021. We also reviewed articles from google scholar. The keywords "ferric carboxymaltose," "FCM," "intravenous," "randomized," "pregnancy," "quality of life," and "neonatal outcomes" were used to search the literature. The search was limited to pregnant women. Selection of studies: Studies related to ferric carboxymaltose in pregnancy were scanned. Observational studies, review articles, and case reports were excluded. Randomized studies in pregnant women involving ferric carboxymaltose and other intravenous iron formulations were shortlisted. Of 256 studies, nine randomized control trials were selected. Data collection: Two reviewers independently extracted data from nine selected trials Data synthesis: The final effect size for increase in hemoglobin after treatment was significant for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 0.89g/dl [95% confidence interval 0.27,1.51]). The final effect size for the increase in ferritin after treatment was more for ferric carboxymaltose vs. iron sucrose/iron polymaltose (standard mean difference 22.53µg/L [-7.26, 52.33]). No serious adverse events were reported with ferric carboxymaltose or other intravenous iron. Conclusion: Ferric carboxymaltose demonstrated better efficacy than other intravenous iron in increasing hemoglobin and ferritin levels in treating iron deficiency anemia in pregnant women.

Coenzyme Q10 in Male and Female Infertility

Infertility is a medical condition that can cause psychological, physical, mental, spiritual, and medical detriments to the patient. Infertility can also be a marker of an underlying chronic disease associated with infertility. It is currently affecting one out of six couples worldwide. The pathophysiology of male and female infertility is multifactorial and still not fully elucidated. Both are related to an imbalance between the production of Reactive Oxygen Species (ROS) and antioxidant defences. Antioxidants are biological and chemical compounds that are synthesized endogenously or exogenously, counteract oxidative stress and act as free radical scavengers. Coenzyme Q10 (CoQ10) is a lipidsoluble quinone acting as an effective antioxidant, which prevents lipid peroxidation and DNA oxidation. It empowers the body’s energy production cycle through Adenosine Triphosphate (ATP) synthesis and has long been used to ameliorate infertility outcomes. Evidence suggests that CoQ10 shows beneficial effects on semen quality, quantity, and mobility in male infertility. Moreover, the potential benefits of oral antioxidants on female infertility treatment are being increasingly investigated, including CoQ10. CoQ10 treatment significantly increases fertilization rate, the number of high-quality embryos, and higher clinical pregnancy and live birth rates. Furthermore, CoQ10 administration enhances ovarian response to stimulation and improves oocyte and embryo quality. Hence, available evidence and clinical studies suggest that CoQ10 supplementation could be considered an inexpensive, safe therapy to enhance infertility treatment in men and women of reproductive age

Establishment of an in vitro plantlet regeneration protocol for unique varieties of brinjal (Solanum melongena L.) var. Mattu Gulla and Perampalli Gulla.

Brinjal (Solanum melongena L.) var. Mattu Gulla (MG) and var. Perampalli Gulla (PG) are unique varieties with distinct flavour cultivated in Udupi, Karnataka State, and are exposed to several biotic and abiotic stresses. An efficient and reproducible in vitro regeneration method is required to expedite the manipulation of these brinjal varieties to cope up with stress by tissue culture and gene transfer methods. The present study, reports a rapid and efficient in vitro regeneration protocol for these two varieties. The in vitro growth response was studied on Murashige and Skoog (MS) medium supplemented with 2, 4-D, BAP and IAA, and the plantlets were regenerated efficiently from callus cultures of leaf, cotyledon and hypocotyl explants. Among the three explants, the hypocotyl explants were found to have better callus induction and multiple shoot regeneration. High frequency of shoot initiation was achieved from hypocotyl derived calluses in MS media with 2.0 mg/L BAP and 0.5 mg/L IAA in MG and PG. Efficient and rapid shoot proliferation, and elongation were noted in MS medium with 1.0 mg/L BAP and 0.3 mg/L GA3. The in vitro regenerated shoots produced healthy roots when they were cultured on MS medium supplemented with 0.5 mg/L IBA. A significant difference was observed in percentage of callus induction, number of shoots per callus, shoot elongation and number of hardened plantlets of MG and PG. MG showed maximum response in all stages of culture than PG. Hardening of plantlets in tissue culture was achieved in three weeks. The hardened plantlets were grown in pots for further acclimatization in green house and finally transplanted to experimental garden where they developed into flowering plants and produced mature fruits with viable seeds.

Genetic variation in genes involved in folate and drug metabolism in a south Indian population.

BACKGROUND: Genetic variations represented as single nucleotide polymorphisms (SNPs) vary across the world population. This genetic polymorphism (such as SNPs) plays an important role in pharmacogenomics. SNPs that affects cellular metabolism, by altering the enzyme activity, have an important role in therapeutic outcome. Allele frequencies in number of clinically relevant SNPs within south Indian populations are not yet known. Hence, we genotyped randomly selected unrelated south Indian subjects from different locations of south India representing the heterogeneous ethnic background of the population. MATERIALS AND METHODS: Common variants of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULT1A1 gene polymorphisms were screened from healthy unrelated south Indian volunteers. Genotypes were determined using RFLP analysis of polymerase chain reaction-amplified products and confirmed by DNA sequencing. Chi-square test was performed to test for deviation from the Hardy-Weinberg equilibrium for each locus. RESULTS: Gene allele frequency for several polymorphisms in our study differed significantly between the populations of other nations reported for several of the SNPs. These results demonstrate that the populations in different geographic regions may have widely varying genetic allele frequencies for clinically relevant SNPs. CONCLUSION: The present study reports, for the first time, the frequency distribution of MTHFD1, TYMS, SHMT1, MTR, MTRR, CBS and SULTIA1 gene polymorphisms in a south Indian population. Population-specific genetic polymorphism studies will help in practicing pharmacogenomic principles in the clinics.

Studies on Brahma rasayana in male swiss albino mice: Chromosomal aberrations and sperm abnormalities.

Ayurveda, the Indian holistic healthcare system encompasses traditional medicines with a principle of creating harmony and maintaining balance within the natural rhythms of the body. Rasayana is one of the branches of Ayurveda frequently used as rejuvenant therapy to overcome many discomforts and prevent diseases. It has been reported that rasayanas have immunomodulatory, antioxidant and antitumor functions. However, the genotoxic potential of many rasayanas remains to be evaluated. The present study was undertaken to assess the role of Brahma rasayana(BR) on genotoxicity in vivo in a mouse test system. The older mice (9 months) were orally fed with rasayana for 8 weeks. The treated groups showed no signs of dose-dependent toxicity at the dosage levels tested. The body weight loss/gain and feed consumption were unaffected at tested doses. Furthermore, sperm abnormalities and chromosomal aberrations were insignificant in the treatment group when compared to controls. However, there was a marginal increase in sperm count in the BR treated animals. These findings clearly indicate that there are no observed adverse genotoxic effects elicited by BR in experimental animals such as mice.

MTHFR Gene variants C677T, A1298C and association with Down syndrome: A Case-control study from South India.

BACKGROUND: The 5,10-methylenetetrahydrofolate reductase (MTHFR) polymorphisms and low folate levels are associated with inhibition of DNA methyltransferase and consequently DNA hypomethylation. The expanding spectrum of common conditions linked with MTHFR polymorphisms includes certain adverse birth outcome, pregnancy complications, cancers, adult cardiovascular diseases and psychiatric disorders, with several of these associations remaining still controversial. Trisomy 21 or Down syndrome (DS) is the most common genetic cause of mental retardation. It stems predominantly from the failure of chromosome 21 to segregate normally during meiosis. Despite substantial research, the molecular mechanisms underlying non-disjunction leading to trisomy 21 are poorly understood. MATERIALS AND METHODS: Two common variants C677T and A1298C of the MTHFR gene were screened in 36 parents with DS children and 60 healthy couples from Tamil Nadu and Karnataka. The MTHFR genotypes were studied by RFLP analysis of PCR-amplified products and confirmed by sequencing. RESULTS: The CT genotype was seen in three each (8.3%) of case mothers and fathers. One case father showed TT genotype. All the control individuals exhibited the wild type CC genotype. A similar frequency for the uncommon allele C of the second polymorphism was recorded in case mothers (0.35) and fathers (0.37) in comparison with the control mothers (0.39) and fathers (0.37). CONCLUSION: This first report on MTHFR C677T and A1298C polymorphisms in trisomy 21 parents from south Indian population revealed that MTHFR 677CT polymorphism was associated with a risk for Down syndrome.

Down syndrome child with 48,XXY,+21 karyotype.

Cytogenetic analysis in 60 clinically suspected cases of Down syndrome and their parents was carried out using conventional Giemsa-trypsin-banding technique. Fifty-five individuals (91%) exhibited a free trisomy 21. Robertsonian translocations were seen in three cases and two cases exhibited a normal karyotype. A four-month-old child, the second-born of non-consanguineous parents, possessed an extra X chromosome in addition to trisomy 21. The proband's parents and his brother showed a normal karyotype. The phenotypic characteristics of this child have been discussed in the light of the published reports on double aneuploidies of XXY and trisomy 21.

Trisomy 4p and partial monosomy 18q due to paternal translocation t(4;18) (p11; q21.3).

A carrier status for balanced translocation in either of the parents increases the risk of congenital malformation in the offspring. A case of multiple congenital anomalies in a female newborn was found to be associated with trisomy 4p and partial monosomy 18q as a result of a reciprocal translocation, t(4; 18) (p11; q21.3) in the father. The clinical and cytogenetic findings are compared with characteristic features of trisomy 4p, monosomy 18q and two similar cases reported earlier.

A Bisatellited Supernumerary Marker Chromosome Associated With Recurrent Miscarriages.

(RSAs) revealed the presence of a supernumerary, metacentric, bisatellited microchromosome marker in the male partner. His karyotype was 47,XY,+mar. Molecular analysis revealed the marker to be an idic 14 or 22 (q11-12). We herein discuss two aspects with respect to the presence of the marker: firstly, the karyotype-phenotype relationship in the carrier as well as the possibility of the marker causing abnormality in the next generation and, secondly, the possible role of the marker in the causation of RSAs.

New evidence of non seasonal factors in the menarche rhythm

The phylogenetic, ontogenetic and seasonal hypotheses on the annual periodicity of menarche were tested. Data from European, Asian (Caucasian, Mongolian and Caucaso-Mongolian people from the northern hemisphere) and Chilean (Caucaso-Amerindian from the southern hemisphere) populations were compared with data from Hungary (Caucaso-Mongolian Europeans from a northern temperature zone) and Madras, India (a complex ethnically originated people from a tropical northern area). Chileans were compared with those Caucaso-Mongolian people because Amerindians belong also to the Mongolian group. Hungarian girls showed peaks of menarche in the month of January (winter), June, July and August (summer), in contradiction with most European Caucasians who showed peaks only in winter months; and in agreement with Finns who showed both peaks. Indian girls had peaks in April, May and June (summer) and more extreme peaks and troughs than the Finnish girls (from a temperature arctic zone). These findings do not agree with the seasonal hypothesis, but they do with the phylogenetic hypothesis. Indian girls had a peak of menarche in the same month of birth and the arrangement of data according to the gestational-menarche coincidence showed a significant heterogeneity for the monthly peaks of menarche; thus, the ontogenetic hypothesis was also supported

Thoracic stomach: comparative evaluation of endoscopy, gastric aspirate analysis and hepatobiliary scintigraphy in the diagnosis of duodeno-gastric reflux.

Twenty patients with thoracic stomach were subjected to hepatobiliary scintigraphy for the diagnosis of duodenogastric reflux. The results of the radionuclide studies were correlated with those of endoscopy and biochemical estimation of total intragastric bile acid. Hepatobiliary scintigraphy was found to be more sensitive (91.6%) and accurate (95%) than endoscopy (25% and 55% respectively) and biochemical estimation of total intragastric bile acid content (66.6% and 80% respectively). Being noninvasive and physiological, radionuclide study appears suitable for routine clinical use in the diagnosis of duodeno-gastric reflux.

Radionuclide detection of gastroesophageal reflux in children suffering from recurrent lower respiratory tract infection.

Radionuclide gastro-esophageal scintigraphy was performed on 25 control and 183 children suffering from recurrent lower respiratory tract infection. Gastro-esophageal reflux (GER) of varying grades was observed in 135 patients. The severity of clinical symptoms in the patients was found to be directly related to the severity of reflux observed in the radionuclide study. In some patients an attempt was also made to quantitate GER by calculating the Gastro-esophageal reflux index. The results of the scintigraphic study were correlated with the results of the other commonly used and more conventional Barium swallow and fluoroscopy study. Gastro-esophageal scintigraphy was found to be much superior in terms of sensitivity, specificity and accuracy in detecting GER. It was also possible to objectively evaluate and monitor response to treatment following conservative or corrective surgical therapy using the radionuclide technique. The results of the study demonstrated a remarkably high incidence of GER in the patients. Whether GER is the cause of recurrent lower respiratory tract infection or not is difficult to establish firmly. But within the preview of the study the association seems to be very strong and cannot be easily ignored.

Significance of transplant perfusion index in the diagnosis of acute rejection in live related renal allograft recipients.

The study was undertaken to assess the usefulness of transplant perfusion index (TPI) in the differential diagnosis of renal allograft dysfunction with special reference to acute rejection. It was observed that the TPI has a sensitivity of 100 per cent and specificity of 98.1 per cent in the diagnosis of acute rejection. It was also observed that the serial values of TPI provided valuable clues and guide in the management of transplant dysfunction and helped in the immediate and long term follow-up of patients with renal allografts.

Profile of thyroid disorders in a referral centre in north India.

From 1983-88, 157 patients were investigated in our clinic for thyroid disorders: 117 (75%) were hypothyroid, 10 (6%)-hyperthyroid, and 30 had euthyroid goiters. Average age of presentation of congenital hypothyroids was 4.07 years. Children with goitrous hypothyroidism (n = 19) were divided into: (i) thyroiditis: RAIU low and patchy, TMA positive: 2 children; (ii) dyshormonogenesis: RAIU high, family history positive, perchlorate discharge test positive: 2 children; (iii) iodine deficiency: RAIU high, urinary iodine low: 2 children, and (iv) cause unknown: RAIU normal or high, other investigations normal: 13 children. Ninety eight hypothyroid children without goiter were divided into 6 groups: (i) athyreosis: RAIU low, no thyroid tissue identifiable (n = 39); (ii) hypoplasia: RAIU low, gland small, in normal position (n = 7); (iii) ectopia: RAIU low, gland in ectopic position (n = 24); (iv) thyroiditis: TMA positive (n = 2); (v) iodine deficiency: low urinary iodine (n = 1); and (vi) cause unknown: RAIU and scan normal, other investigations normal and not done (n = 8). Proportionate short stature was present in 44.4% children. Twenty two children presented only with growth failure; 72% of them had dysgenetic glands. Early onset marked the group with hyperthyroidism (n = 10). Euthyroid goiter was present in 30 (19%). Hypothyroidism is still being diagnosed very late. All children with growth failure, even if proportionate, must have thyroid status evaluated.

Beneficial effect of oral verapamil on exercise induced silent myocardial ischemia.

Twelve consecutive patients (all males, age 40-72 years) of asymptomatic angiographically proven coronary artery disease who showed exercise induced regional wall motion abnormalities (RWMA) on Radionuclide Ventriculography were restudied by the same method after 208 weeks treatment with oral Verapamil 240 mg/day. Resting and peak exercise global ejection fractions and RWMA were compared using paired t-test. Without verapamil therapy, the resting mean ejection fraction was 64.75% (SD 9.45%), and fell with exercise (mean fall 5.25%, range - 25% to + 4%). On Verapamil therapy, the resting ejection fraction was 62.75% (SD 8.35%), and rose with exercise (mean rise 1.18%, range - 24% to + 18%). These changes in exercise ejection fractions with and without verapamil therapy were statistically significant (p = 0.01). Four of 5 resting, and 8 of 15 peak exercise induced RWMA improved on therapy. There were no significant differences in resting or peak-exercise double products with and without verapamil. We conclude that oral verapamil improves exercise induced ventricular dysfunction and regional wall motion abnormalities in patients with silent myocardial ischemia.

Genetic analysis of a group of mentally retarded children.

Genetic analysis of 169 mentally retarded (MR) children from Madras, revealed chromosomal abnormalities in 17%. Down syndrome was the major chromosomal anomaly (24/169 = 14.2%). These included three cases of trisomy-21 mosaics, and one case of de novo Robertsonian translocation. MR children with chromosomal abnormalities were either mildly or moderately retarded. Syndromes with known etiology occurred in 3% of the MR cases. Microcephaly, neonatal anoxia, perinatal stress and pharmacological attempt for abortion were found to be important pathogenic factors associated with MR. Most of the microcephalics (11/169 = 6.5%) were severely retarded, whereas those associated with neonatal anoxia and perinatal stress were either mildly or moderately retarded. Birth-order effects were found only among Down syndrome patients. Segregation analysis of the three groups of proband families (viz. mild, moderate and severe MR) indicated that autosomal recessive mode of inheritance is compatible in moderate and severe MR proband families. The proportion of X-linked instances of MR is estimated to be about 22% of the cases.