Hepatoprotective studies on Hedyotis corymbosa (L.) Lam

Hedyotis corymbosa is used in traditional medicine of India and China to treat various hepatic disorders. In the present study, the hepatoprotective effect of the methanolic extract of the whole plant of Hedyotis corymbosa against paracetamol overdose-induced liver damage in Wistar rats was studied. The methanolic extract of the plant produced significant hepatoprotective effects as evidenced by decreased serum enzyme activities, SGPT, SGOT, SAKP and serum bilirubin and an almost normal histological architecture of the liver, in treated groups, compared to the controls. Hedyotis corymbosa shortened hexobarbitone-induced sleeping time in mice, besides showing significant antilipid peroxidant effect in vitro. The results thus support the use of Hedyotis corymbosa as a hepatoprotective agent.     

Autosomal dominant late-onset spinal motor neuronopathy is linked to a new locus on chromosome 22q11.2-q13.2

Spinal muscular atrophies (SMAs) are hereditary disorders characterized by degeneration of lower motor neurons. Different SMA types are clinically and genetically heterogeneous and many of them show significant phenotypic overlap. We recently described the clinical phenotype of a new disease in two Finnish families with a unique autosomal dominant late-onset lower motor neuronopathy. The studied families did not show linkage to any known locus of hereditary motor neuron disease and thus seemed to represent a new disease entity. For this study, we recruited two more family members and performed a more thorough genome-wide scan. We obtained significant linkage on chromosome 22q, maximum LOD score being 3.43 at marker D22S315. The linked area is defined by flanking markers D22S686 and D22S276, comprising 18.9 Mb. The region harbours 402 genes, none of which is previously known to be associated with SMAs. This study confirms that the disease in these two families is a genetically distinct entity and also provides evidence for a founder mutation segregating in both pedigrees.     

Co-segregation of DM2 with a recessive CLCN1 mutation in juvenile onset of myotonic dystrophy type 2

Myotonic dystrophy type 2 (DM2) is a common adult onset muscular dystrophy caused by a dominantly transmitted (CCTG)( n ) expansion in intron 1 of the CNBP gene. In DM2 there is no obvious evidence for an intergenerational increase of expansion size, and no congenital cases have been confirmed. We describe the clinical and histopathological features, and provide the genetic and molecular explanation for juvenile onset of myotonia in a 14-year-old female with DM2 and her affected mother presenting with a more severe phenotype despite a later onset of symptoms. Histological and immunohistochemical findings correlated with disease severity or age at onset in both patients. Southern blot on both muscle and blood samples revealed only a small increase in the CCTG repeat number through maternal transmission. Fluorescence in situ hybridization, in combination with MBNL1 immunofluorescence on muscle sections, showed the presence of mutant mRNA and MBNL1 in nuclear foci; the fluorescence intensity and its area appeared to be similar in the two patients. Splicing analysis of the INSR, CLCN1 and MBNL1 genes in muscle tissue demonstrates that the level of aberrant splicing isoforms was lower in the daughter than in the mother. However, in the CLCN1 gene, a heterozygous mutation c.501C>G p.F167L was present in the daughter's DNA and found to be maternally inherited. Biomolecular findings did not explain the unusual young onset in the daughter. The co-segregation of DM2 with a recessive CLCN1 mutation provided the explanation for the unusual clinical findings.     

New phenotype and pathology features in MYH7-related distal myopathy

Laing distal myopathy is an autosomal dominant disease due to mutations in the gene encoding for the human slow-β myosin heavy chain, MYH7. Most reports describe it as a mild, early onset myopathy with involvement usually restricted to foot extensors, hand finger extensors and neck flexors, and unspecific findings on muscle biopsy. We identified the first two Italian families with Laing distal myopathy, harboring two novel mutations in the MYH7 gene and performed clinical, neurophysiological, pathological, muscle MRI and cardiological investigations on affected members from the two families. Subjects from one family presented a moderate-severe phenotype, with proximal together with distal involvement and even loss of ambulation at advanced age. One patient displayed atypical muscle biopsy findings including cytoplasmic bodies and myofibrillar myopathy-like features. Affected members from the second family shared a very mild phenotype, with weakness largely limited to long toe and foot extensors and/or late onset. No patient showed any sign of heart involvement. Our study significantly broadens the clinical and pathological spectrum of Laing distal myopathy. We suggest that MYH7 screening should be considered in undiagnosed late-onset distal myopathy or cytoplasmic body myopathy patients.     

Radiation-Related Deregulation of TUBB3 and BRCA1/2 and Risk of Secondary Lung Cancer in Women With Breast Cancer

IntroductionBreast cancer survivors are at increased risk of developing unrelated primary cancers, particularly lung cancer. Evidence indicates that sex hormones as well as a deregulation of DNA-repair pathways may contribute to lung cancer onset. We investigated whether the hormone status and expression of markers involved in DNA repair (BRCA1/2, ERCC1, and P53R2), synthesis (TS and RRM1), and cell division (TUBB3) might be linked to lung cancer risk.Patients and MethodsThirty-seven breast cancer survivors with unrelated lung cancer and 84 control subjects comprising women with breast cancer (42/84) or lung cancer (42/84) were enrolled. Immunohistochemistry on tumor tissue was performed. Geometric mean ratio was used to assess the association of marker levels with patient groups.ResultsEstrogen receptor was expressed in approximately 90% of the breast cancer group but was negative in the majority of the lung cancer group, a result similar to the lung cancer control group. Likewise, ER isoform β was weakly expressed in the lung cancer group. Protein analysis of breast cancer versus control had a significantly lower expression of BRCA1, P53R2, and TUBB3. Likewise, a BRCA1 reduction was observed in the lung cancer group concomitant with a BRCA2 increase. Furthermore, BRCA2 and TUBB3 increased in ipsilateral lung cancer in women who had previously received radiotherapy for breast cancer.ConclusionThe decrease of DNA-repair proteins in breast cancer could make these women more susceptible to therapy-related cancer. The increase of BRCA2 and TUBB3 in lung cancer from patients who previously received radiotherapy for breast cancer might reflect a tissue response to exposure to ionizing radiation.     

Hypersensitivity reactions to antilipemic drugs

Chronic utilization of hipolipemiants drugs makes possible the onset of hypersensitivity reactions like a part of secondary reactions. From the point of our experience the most frequent hyperreactivity appears on fibric acid derivates. Al the cases we treated, were skin manifestations (angioedema) and about 29%, were digestive manifestations (dyspepsia, vomiting, diarrhoea). At the same time, chronic utilization of nicotinic acid derivates favored skin rash due to congestive intrinsic effect of nicotinic acid.     

Anti-inflammatory and analgesic properties of Drynaria quercifolia (L.) J. Smith

Ethnopharmacological relevance

Drynaria quercifolia (L.) J. Smith (Polypodiaceae), has been widely used by ethnic groups of India to treat inflammation, rheumatism, headache, bone fracture, jaundice, etc.

Aim of the study

To evaluate the anti-inflammatory and analgesic properties of the ethanolic extract of rhizome of Drynaria quercifolia (DQ) and its phytochemical profile.

Materials and methods

DQ was used to evaluate the anti-inflammatory and analgesic effects using carrageenan-induced paw oedema/cotton pellet-induced granuloma in Wistar rats and acetic acid-induced writhing/formalin-induced paw licking test in Swiss albino mice respectively.

Results

Oral administration of DQ produced significant inhibition of carrageenan-induced paw oedema and granuloma formation in rats, almost comparable to that caused by indomethacin. DQ significantly attenuated acute and delayed phases of formalin-induced pain and acetic acid-induced writhing episodes in mice. The analgesia was comparable to that produced by sodium salicylate and aspirin respectively. Phytochemical analysis gave positive tests for catechin, coumarins, flavonoids, phenolics, saponin, steroids, tannins, and triterpenes. The total phenolics in DQ was 244 mg/g and naringin content was 0.048%.

Conclusion

The results suggest the presence of potent anti-inflammatory and analgesic principles in DQ that justifies its use for alleviating painful inflammatory conditions.     

Molecular characterization of Capripox viruses obtained from field outbreaks in Nigeria between 2000 and 2016

Capripox virus infections are endemic diseases of livestock in Nigeria, but there are limited data on molecular characterization of circulating viruses. In this study, we investigated field outbreaks of Capripox virus infections in Nigeria via partial sequencing of viruses obtained from field samples. Eleven selected samples, collected from 2000–2016 from cattle (9), sheep (1) and goat (1) in three states in Nigeria and Capripox virus genome positive by PCR and real‐time qPCR, were characterized using our newly developed partial sequencing protocol. This method for genetic characterization of Capripox virus strains allows a first, short molecular classification of strains responsible for the investigated field outbreaks in the country. Phylogenetically, the eight LSDV samples obtained from 2010 to 2016 are closely related to already published strains occurring in Greece and Serbia in the years 2015 and 2016, respectively, whereas the isolate from 2000 shows high similarity to the South African NI‐2490 strain. These data indicate that there was a change of LSDV strains circulating in Nigeria between the years 2000 and 2010. The samples isolated from a goat and a sheep in different years seem to be related to already known GTPV strains, but clearly differ from all current published GTPV strains. Interestingly, both newly detected GTPV strains show up to 100% similarity compared to each other and led to clinical disease in sheep and goats. It is long known that some strains of GTPV and SPPV are able to infect both sheep and goats, but in most cases lead to more severe disease in only one of these species. Further genetic characterization of these isolates could provide more insight into pathogenesis and virulence factors of Capripox viruses, especially GTPV and SPPV.