Human hepatocyte transplantation for liver disease: current status and future perspectives.

Liver transplantation is the accepted treatment for patients with acute liver failure and liver-based metabolic disorders. However, donor organ shortage and lifelong need for immunosuppression are the main limitations to liver transplantation. In addition, loss of the native liver as a target organ for future gene therapy for metabolic disorders limits the futuristic treatment options, resulting in the need for alternative therapeutic strategies. A potential alternative to liver transplantation is allogeneic hepatocyte transplantation. Over the last two decades, hepatocyte transplantation has made the transition from bench to bedside. Standardized techniques have been established for isolation, culture, and cryopreservation of human hepatocytes. Clinical hepatocyte transplantation safety and short-term efficacy have been proven; however, some major hurdles-mainly concerning shortage of donor organs, low cell engraftment, and lack of a long-lasting effect-need to be overcome to widen its clinical applications. Current research is aimed at addressing these problems, with the ultimate goal of increasing hepatocyte transplantation efficacy in clinical applications.

Late cytomegalovirus infection in children: High incidence of allograft rejection and hepatitis in donor negative and seropositive liver transplant recipients.

The complications and outcome associated with late CMV infection and disease on the graft are poorly characterized in PLT recipients. We studied the overall incidence, risk factors, and outcome of late CMV infection and disease (infection 6 months after transplant) in 180 PLT recipients admitted between 2008 and 2011 at the King's College Hospital. Antiviral prophylaxis of intravenous ganciclovir was given only to the D+R- group starting at day 7 post-transplant. The remaining groups (D-R+, D+R+, and D-R-) received pre-emptive therapy when they have CMV viremia above cut-off value and treatment for symptomatic CMV infection. The overall incidence of late CMV infection and disease was 9.4% (19/180) and 14.5% (19/130) in D+R-, D-R+, D+R- groups. The D-R+ group had the highest incidence of hepatitis (37.5%) and significantly increased incidence of CMV disease, and single and multiple acute rejection episodes when compared to the D+R- group, which received prophylaxis. The late CMV infection and disease in pediatric LT recipients was comparable to adult LT recipients despite variable duration of antiviral prophylaxis. Our results show that D-R+ group had highest rate of hepatitis and rejection episodes, associated with high morbidity, and should be considered for antiviral prophylaxis.

Effect of nitrogen fertigation and sowing time on the expression of Cry2Ab and on mortality of Spodoptera litura in Bollgard II cotton.

Toxin expression of Cry2Ab was studied in plant parts of Bollgard II cotton genotype MRC 7031 sown under different treatments of nitrogen application and planting dates. The expression was quantified by using Cry2Aa ELISA kit. Mean per cent mortality of one-day-old, 3rd and 5th instar larvae of Spodoptera litura was observed on different plant parts of MRC 7031 and their respective non-Bt cotton genotypes. The study deduced that mean maximum expression (19.24, 20.93 and 20.71 microg g(-1) in leaves, squares and bolls, respectively) of Cry2Ab was observed at higher nitrogen dose @ 300 kg ha(-1) (N3), while it was minimum (18.67, 20.44 and 20.14 microg g(-1) in leaves, squares and bolls, respectively) at low nitrogen dose @ 150 kg ha(-1) (N1). Studies conducted for different planting dates showed mean maximum expression (18.98, 20.72 and 20.42 microg g(-1) in leaves, squares and bolls, respectively) of Cry2Ab during late sown crop (15th May) as compared to early sown crop (15th April), the expression was 18.66, 20.32 and 20.06 microg g(-1) in leaves, squares and bolls, respectively. Quantitative expression of Cry2Ab was found to vary among different plant parts, i.e more in squares followed by bolls and leaves. Regarding mortality of different instars of S. litura, it was significantly more at higher nitrogen doses and it ranged from 83.04 to 96.27, 53.38 to 61.87 and 16.87 to 22.58% in case of S. litura one-day-old larvae, 3rd and 5th instar, respectively. While, non significant difference in mortalitywas observed during different sowing dates.

Does buprenorphine maintenance improve the quality of life of opioid users?

BACKGROUND & OBJECTIVES: The quality of life (QOL) of substance abusers is known to be severely impaired. Information on impact of opioid maintenance treatment on the QOL of opioid dependent subjects though available from the developed countries, is lacking from India. This study was carried out to assess the impact of buprenorphine maintenance treatment on the quality of life (QOL) of opioid dependent subjects at nine months follow up. METHODS: Based on specified inclusion criteria a total of 231 subjects were recruited from five participating centres across India. They received sublingual buprenorphine as a directly observed therapy along with brief psychosocial intervention (provided in groups of 8-10 subjects) after intake in to the study. The WHOQOL-BREF scale domain scores obtained at baseline were compared to domain scores at nine months follow up. RESULTS: At nine months follow up, among the 64.1 per cent retained in buprenorphine maintenance, there was a significant (P<0.001) decline in opioid use from 24.9 ± 10.1 days at baseline to 1.7 ± 4.7 days at nine months follow up and improvements in score of the four WHOQOL-BREF domains (Physical, Psychological, Social relationships and Environment). INTERPRETATION & CONCLUSIONS: The results showed the beneficial effects of buprenorphine maintenance treatment in improving the QOL of opioid-dependent subjects at nine month follow up. These results point towards the need for an expanded nation-wide provision of buprenorphine maintenance treatment as a harm reduction strategy for the opioid dependent population.

Limitations, progress and prospects of application of biotechnological tools in improvement of bamboo-a plant with extraordinary qualities.

Bamboos (family Poaceae) are the most beautiful and useful plants on the Earth, mainly found in the tropical and sub-tropical regions of the world. Bamboos are fast growing and early maturing, but lack of proper management of bamboo resources is leading to rapid reduction of the existing bamboosetum. Bamboo propagation through seeds is limited due to long flowering cycle of upto 120 years, seed sterility and short seed viability. Infrequent and unpredictable flowering events coupled with peculiar monocarpic behaviour i.e. flowering once before culm death, and extensive genome polyploidization are additional challenges for this woody group. Similarly, vegetative propagation by cuttings, offsets and rhizomes are also inadequate to cope up with the demand of planting stock due to large propagule size, limited availability, seasonal dependence, low multiplication rate and rooting percentage. Therefore, attempts have been made to propagate bamboos through in vitro techniques. In vitro flowering has also been achieved successfully in some bamboo species. Classification systems proposed to date need further support, as taxonomic delineation at lower levels is still lacking sufficient resolution. Tremendous advancement in molecular markers holds the promise to address the needs of bamboo taxonomy (systematics and identification) and diversity studies. Successful application of molecular marker techniques has been achieved in several bamboo species although, more studies are required to understand the population structure and genetic diversity of bamboos in a better way. In addition, some efforts have also been made to clone important genes from bamboos and also for genetic transformation using Agrobacterium and particle bombardment methods. An overview of the recent developments made in improvement of bamboos through in vitro propagation, molecular marker technologies, cloning, and transformation and transgenics has been presented. The future potential of improvement of bamboos using modern biotechnological tools has also been discussed.

Oral lesions in leprosy revisited: a case report.

There is a scarcity of the histopathologically proven lesions of leprosy in the oral cavity, in the world literature. A 55-year-old man had come with a complaint of asymptomatic nodular lesions in the oral cavity. Cutaneous lesions and peripheral nerve examination were suggestive of lepromatous leprosy. Histopathologic examination of a nodule on the palate demonstrated diffuse macrophagic granulomas and acid-fast bacilli.

Oral health status of a group of illicit drug users in Delhi, India.

OBJECTIVES: To assess the oral health and related practices of a group of illicit drug users in Delhi, India; to compare with that of non-drug users; and to assess the impact of illicit drug use on oral health. DESIGN: Cross-sectional study. Comparison was made with non-drug users to investigate any differences in oral health between illicit drug users and general population. SETTING AND PARTICIPANTS: Illicit drug users attending a drug dependence treatment clinic in Delhi (n=126). Equal number of non-drug users attending other outpatient departments in the same setting. OUTCOME MEASURES: Oral health practices assessed using structured questionnaire; dental caries, periodontal status and oral mucosa assessed using World Health Organization 2004 criteria; oral hygiene assessed using OHI-S. RESULTS: Mean DMFT and OHI-S scores amongst the drug users were 3.48 and 3.80, respectively. Bleeding, shallow pockets and deep pockets were found as the highest CPI finding in 42%, 44% and 12% of drug users respectively. Premalignant states of leukoplakia and OSMF were diagnosed in 13% and 4% of drug users respectively. Significant differences were found between drug users and non-drug users with respect to oral hygiene practices; DMFT, OHI-S, CPI scores; and leukoplakia. In multivariate analysis, illicit drug use was significantly associated with CPI highest score (OR = 2.21, 95% CI 1.08-4.52). CONCLUSION: The illicit drug users had significantly poorer oral hygiene practices, oral hygiene and periodontal health; higher caries experience; and higher prevalence of leukoplakia as compared to non-drug users. The findings of the study suggest that illicit drug use is independently associated with poor periodontal health.

Correction to: Patient-Specific Mandibular Reconstruction Plates Increase Accuracy and Long-Term Stability in Immediate Alloplastic Reconstruction of Segmental Mandibular Defects.

[This corrects the article DOI: 10.1007/s12663-019-01323-9.].

Deep UV nano-microstructuring of substrates for surface plasmon resonance imaging.

In this paper, we describe wafer-scale fabrication and characterization of plasmonic chips-containing different sizes and spacings of metallic micro- and nanoline structures-using deep UV lithography. Using a high dose (25 mJ cm( - 2)) and a proper lift-off process, feature sizes as small as 25 nm are obtained. Moreover, we study the dependence of surface plasmon resonance on the angle of incidence and wavelength for different micro- and nanoline size and spacing values, yielding localized to quasi-propagative plasmonic behaviors. Rigorous coupled wave analysis (RCWA) techniques are employed to numerically confirm these experimental observations. Finally, the refractive index of media around the SPRI sensor chips is varied, showing the angulo-spectral regions of higher sensitivity for each type of structure.

Local delivery of interleukin 4 by retrovirus-transduced T lymphocytes ameliorates experimental autoimmune encephalomyelitis.

Experimental autoimmune encephalomyelitis (EAE) is an inflammatory autoimmune disease of the central nervous system which serves as a model for the human disease multiple sclerosis. We demonstrate here that encephalitogenic T cells, transduced with a retroviral gene, construct to express interleukin 4, and can delay the onset and reduce the severity of EAE when adoptively transferred to myelin basic protein-immunized mice. Thus, T lymphocytes transduced with retroviral vectors can deliver "regulatory cytokines" in a site-specific manner and may represent a viable therapeutic strategy for the treatment of autoimmune disease.

Bilirubin, a physiological antioxidant, can improve cryopreservation of human hepatocytes.

The availability of cryopreserved hepatocytes is required for a more widespread use of hepatocyte transplantation, but human hepatocytes are easily damaged during freezing-thawing. Here, preincubation with unconjugated bilirubin, a physiological antioxidant, resulted in increased viability and function of hepatocytes (as determined by trypan blue exclusion, mitochondrial succinate dehydrogenases activity, urea synthesis, and cytochrome P450 1A/2) compared with cells incubated without the pigment. These findings suggest that unconjugated bilirubin may be used as cryoprotectant in clinical hepatocyte transplantation.

Patient-Specific Mandibular Reconstruction Plates Increase Accuracy and Long-Term Stability in Immediate Alloplastic Reconstruction of Segmental Mandibular Defects.

OBJECTIVES: The aim of the current study was to evaluate potential differences in the accuracy of mandibular reconstruction and long-term stability, with respect to different reconstructive procedures. METHODS: In total, 42 patients who had undergone primary segmental mandibular resection with immediate alloplastic reconstruction, with either manually pre-bent or patient-specific mandibular reconstruction plates (PSMRP), were included in this study. Mandibular dimensions, in terms of six clinically relevant distances (capitulum [most lateral points], capitulum [most medial points], incisura [most caudal points], mandibular foramina, coronoid process [most cranial points], dorsal tip of the mandible closest to the gonion point) determined from tomographic images, were compared prior to, and after surgery. RESULTS: Dimensional alterations were significantly more often found when conventionally bent titanium reconstruction plates were used. These occurred in the area of the coronoid process (p = 0.014). Plate fractures were significantly (p = 0.022) more often found within the manually pre-bent group than within the PSMRP group (17%/0%). CONCLUSION: The results suggest that the use of PSMRP may prevent rotation of the proximal mandibular segment, thus avoiding functional impairment. In addition, the use of PSMRP may potentially enhance the long-term stability of alloplastic reconstructions.

Study of the factors affecting health-related quality of life in adolescents after liver transplantation.

The aim of the study was to identify factors affecting health-related quality of life (HRQL) in adolescents after liver transplantation. HRQL was measured using the CHQ-CF87 in 55 adolescents, aged 12-18 years. Factors associated with HRQL included allograft morbidity, psychological and family-related variables measured through standardized questionnaires. The domains of the CHQ-CF87 were reduced using factor analysis to give physical, psychological and social domains. Impacting factors were identified through stepwise, multiple regression analysis. Adolescents had significantly lower HRQL in every domain except for role/social-behavior and family cohesion compared to the general population. Adolescents experienced median 18 (range 4-31) symptoms related to immunosuppression, 40(75%) had one or more chronic illnesses related to immunosuppression and 12(22%) had a history of emotional difficulties. Self-esteem and emotional health were similar to the general population but behavior and aspects of family function were lower. Following regression analysis, the factors associated with HRQL were: age at transplant, secondary chronic illness, symptom distress, headaches, history of emotional difficulties, self-esteem and family conflict. These explained 57% of the variance in physical function, 61% of psychological function and 39% of social function. HRQL is significantly reduced in adolescents after transplantation, which could be related to immunosuppression and psychosocial factors.

Human hepatocyte transplantation: state of the art.

Hepatocyte transplantation is making its transition from bench to bedside for liver-based metabolic disorders and acute liver failure. Over eighty patients have now been transplanted world wide and the safety of the procedure together with medium-term success has been established. A major limiting factor in the field is the availability of good quality cells as hepatocytes are derived from grafts that are deemed unsuitable for transplantation. Alternative sources of cell, including stem cells may provide a sustainable equivalent to primary hepatocytes. There is also a need to develop techniques that will improve the engraftment, survival and function of transplanted hepatocytes. Such developments may allow hepatocyte transplantation to become an accepted and practical alternative to liver transplantation in the near future.

DNA integrity and semen quality in men with low seminal antioxidant levels.

Accurate transmission of information coded in the sperm genome is vital to the pre- and post-natal development of the offspring. Recent advances in reproductive biology have proposed evaluation of sperm DNA integrity as an important assessment tool to infer the presence of DNA strand breaks, numerical abnormalities in sperm chromosome complement, and alterations in the epigenetic regulation of the paternal genome. Oxidative stress (OS), characterized by increased free radicals, may lead to the production of apurine sites, apyrimidine sites, oxidation of nucleotides of sperm genome. This study was performed to assess the impact of OS on DNA integrity in sperms. 52 infertile men [oligozoospermic-13, asthenozoospermic-15, teratozoospermic-19, oligoasthenoteratozoospermic-5] and 20 fertile controls were investigated for products of lipidperoxides as malondialdehyde; antioxidants such as superoxide dismutase, catalase and glutathione in seminal plasma by biochemical methods. DNA integrity of the sperms was analyzed by visual scoring method in which the comets were graded into 4 categories (A-D) on the basis of their tail length indicative of increasing levels of DNA damage. Significant increase in DNA damage (higher number of sperms in group D) in cases (oligozoospermic (O)-20%, asthenozoospermic (A)-24%, teratozoospermic (T)-28%, OAT-43%) as compared to controls (8%) was found. Increased malondialdehyde levels, abnormal sperm morphology and higher DNA damage were observed in the cases. The antioxidants superoxide dismutase, catalase and glutathione had a positive association with sperm count and motility while a negative association with the percentage of dead sperms and abnormal morphology was observed. This study highlights the influence of low antioxidants on sperm genome integrity and indicates sperm DNA integrity as a better and more reliable prognostic tool for infertility evaluation than simple quantitative and morphologic evaluation of spermatozoa.

Role of ascorbic acid in human seminal plasma against the oxidative damage to the sperms.

This study evaluated the extent of oxidative stress by measuring malondialdehyde and ascorbic acid in the seminal plasma of human subjects with different fertility potential. Semen samples from 148 subjects were evaluated (48 normozoospermics, 34 oligoasthenoteratozoospermics, 34 asthenoteratozoospermics and 32 azoospermics). malondialdehyde level was found to be significantly higher in the abnormal groups (oligoasthenoterato and asthenoterato-zoospermics) than normozoospermics (P < 0.01). Negative correlation was also found between malondialdehyde level, sperm concentration, sperm motility and sperm morphology. Level of ascorbic acid was found to be significantly higher in normozoospermics than other abnormal groups (P < 0.01). It was found to be correlated positively with all seminogram parameters and negatively with malondialdehyde level. The study revealed that, excess lipid peroxidation reflected by high malondialdehyde level with reduced ascorbic acid in human seminal plasma is associated with poor semen quality where as ascorbic acid content has positive correlation with fertility potential.

Substance use among treatment seeking Indian adolescent girls: Are they unique?

INTRODUCTION: Substance use among adolescents is on the rise across the globe along with a diminution of gender gap observed earlier posing a huge public health burden. Unfortunately, there is a paucity of literature on adolescent substance use. The literature is even sparse about substance use among adolescent girls. The current study aims to provide a glimpse of the profile and pattern of substance use among Indian adolescent girls seeking treatment for substance use problems in a specialty addiction treatment centre in India. MATERIALS AND METHODS: This study is retrospective in design. Information regarding socio-demographics and substance use were extracted from the medical records of adolescent girls (≤ 19 years) who sought treatment for substance use problems during 2004-2018, at the adolescent clinic of a tertiary addiction treatment centre located in north India was retrieved carried out. The data was statistically analysed using SPSS. RESULTS: A total of 28 girls sought treatment during this period. The mean age of the girls was 15.89 ± 2.72 years. Most of the girls were students (6/28) or had never started working (12/28). Majority of them were coming from an urban background (89.3%) and were educated up to 10th class (85.5%). A total of 17 (60.7%) girls sought treatment for opioids use of which 11 were using illicit opioids like heroin and five (29.9%) of them reported taking opioids by injecting route primarily. History of past abstinence attempts, and treatment attempt were present in very few of them (10.7% and 14.3%). CONCLUSION: Our study suggests a distinct substance use profile of adolescent girls. There is a need for further systematic studies to assess their clinical needs.

Hepatocyte transplantation followed by auxiliary liver transplantation--a novel treatment for ornithine transcarbamylase deficiency.

We report the first successful use of hepatocyte transplantation as a bridge to subsequent auxiliary partial orthotopic liver transplantation (APOLT) in a child antenatally diagnosed with severe ornithine transcarbamylase (OTC) deficiency. A total of 1.74 x 10(9) fresh and cryopreserved hepatocytes were administered intraportally into the liver over a period of 6 months. Immunosuppression was with tacrolimus and prednisolone. A sustained decrease in ammonia levels and a gradual increase in serum urea were observed except during episodes of sepsis in the first 6 months of life. The patient was able to tolerate a normal protein intake and presented a normal growth and neurological development. APOLT was successfully performed at 7 months of age. We conclude that hepatocyte transplantation can be used in conjunction with APOLT as an effective treatment for severe OTC-deficient patients, improving neurodevelopmental outcomes.