Targeting senescent hepatocytes using the thrombomodulin-PAR1 inhibitor vorapaxar ameliorates NAFLD progression.

BACKGROUND AND AIMS: Senescent hepatocytes accumulate in parallel with fibrosis progression during NASH. The mechanisms that enable progressive expansion of nonreplicating cell populations and the significance of that process in determining NASH outcomes are unclear. Senescing cells upregulate thrombomodulin-protease-activated receptor-1 (THBD-PAR1) signaling to remain viable. Vorapaxar blocks the activity of that pathway. We used vorapaxar to determine if and how THBD-PAR1 signaling promotes fibrosis progression in NASH. APPROACH AND RESULTS: We evaluated the THBD-PAR1 pathway in liver biopsies from patients with NAFLD. Chow-fed mice were treated with viral vectors to overexpress p16 in hepatocytes and induce replicative senescence. Effects on the THBD-PAR1 axis and regenerative capacity were assessed; the transcriptome of p16-overexpressing hepatocytes was characterized, and we examined how conditioned medium from senescent but viable (dubbed "undead") hepatocytes reprograms HSCs. Mouse models of NASH caused by genetic obesity or Western diet/CCl 4 were treated with vorapaxar to determine effects on hepatocyte senescence and liver damage. Inducing senescence upregulates the THBD-PAR1 signaling axis in hepatocytes and induces their expression of fibrogenic factors, including hedgehog ligands. Hepatocyte THBD-PAR1 signaling increases in NAFLD and supports sustained hepatocyte senescence that limits effective liver regeneration and promotes maladaptive repair. Inhibiting PAR1 signaling with vorapaxar interrupts this process, reduces the burden of 'undead' senescent cells, and safely improves NASH and fibrosis despite ongoing lipotoxic stress. CONCLUSION: The THBD-PAR1 signaling axis is a novel therapeutic target for NASH because blocking this pathway prevents accumulation of senescing but viable hepatocytes that generate factors that promote maladaptive liver repair.

The mechanism of acute fasting-induced antidepressant-like effects in mice.

Acute fasting induced antidepressant-like effects. However, the exact brain region and mechanism of these actions are still largely unknown. Therefore, in this study the antidepressant-like effects of acute fasting on c-Fos expression and BDNF levels were investigated. Consistent with our previous findings, immobility time was remarkably shortened by 9 hrs fasting in the forced swimming test. Furthermore, these antidepressant-like effects of 9 fasting were inhibited by a 5-HT2A/2C receptor agonist (±)-1-(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), and the effect of DOI was blocked by pretreatment with a selective 5-HT2A receptor antagonist ketanserin. Immunohistochemical study has shown that c-Fos level was significantly increased by 9 hrs fasting in prefrontal cortex but not hippocampus and habenular. Fasting-induced c-Fos expression was further enhanced by DOI in prefrontal cortex, and these enhancements were inhibited by ketanserin. The increased BDNF levels by fasting were markedly inhibited by DOI in frontal cortex and hippocampus, and these effects of DOI on BDNF levels were also blocked by ketanserin. These findings suggest that the antidepressant-like effects of acute fasting may be exerted via 5-HT2A receptor and particularly sensitive to neural activity in the prefrontal cortex. Furthermore, these antidepressant-like effects are also mediated by CREB and BDNF pathway in hippocampus and frontal cortex. Therefore, fasting may be potentially helpful against depression.

Cost Analysis of Initial Treatment With Endovascular Revascularization, Open Surgery, or Primary Major Amputation in Patients With Peripheral Artery Disease.

PURPOSE: To compare the total initial treatment costs for open surgery, endovascular revascularization, and primary major amputation within a single-payer healthcare system. METHODS: A multicenter, retrospective analysis was undertaken to evaluate 1138 patients with symptomatic peripheral artery disease (PAD) who underwent 1017 endovascular procedures, 86 open surgeries, and 35 major amputations between 2013 and 2016. A cost-mix analysis was performed on individual patient data generated for selected diagnosis-related groups. Mean costs are presented with the 95% confidence interval (CI). RESULTS: There was no intergroup difference in demographics or private health insurance status. However, the amputation group had a higher proportion of emergency procedures (68.6% vs 13.3% vs 27.9%, p<0.001) and critical limb ischemia (88.6% vs 35.9% vs 37.2%, p<0.001) compared with the endovascular therapy and open surgery groups, respectively. The endovascular revascularization group spent less time in hospital and used fewer intensive care unit (ICU) resources compared with the open surgery and major amputation groups (hospital length of stay: 3.4 vs 10.0 vs 20.2 days, p<0.01; ICU: 2.4 vs 22.6 vs 54.6 hours, p<0.01), respectively. While mean prosthetic and device costs were higher in the endovascular group [AUD$2770 vs AUD$1658 (open) and AUD$1219 (amputation), p<0.01], substantial disparities were observed in costs associated with longer operating theater times, length of stay, and ICU utilization, which resulted in significantly higher costs in the open and amputation groups. After adjusting for confounders, the AUD$18,396 (95% CI AUD$16,436 to AUD$20,356) mean cost per admission for the endovascular revascularization group was significantly less (p<0.001) than the open surgery (AUD$31,908, 95% CI AUD$28,285 to AUD$35,530) and major amputation groups (AUD$43,033, 95% CI AUD$37,706 to AUD$48,361). CONCLUSION: Endovascular revascularization procedures for PAD cost the health payer less compared with open surgery and primary amputation. While devices used to deliver contemporary endovascular therapy are more expensive, the reduction in bed days, ICU utilization, and related hospital resources results in a significantly lower mean total cost per admission for the initial treatment.

Clinical disease activity, C-reactive protein normalisation and mucosal healing in Crohn's disease in the SONIC trial.

BACKGROUND AND AIMS: The Crohn's Disease Activity Index (CDAI) has been criticised due to heavy weighting on subjective clinical symptoms. C-reactive protein (CRP) and endoscopic lesions are objective measures of inflammation. We investigated the relationships between clinical disease activity, CRP normalisation and mucosal healing in Crohn's disease (CD). METHODS: The Study of Biologic and Immunomodulator Naive Patients in CD trial compared infliximab to azathioprine and to infliximab plus azathioprine in 508 CD patients. Mucosal healing was defined as the absence of mucosal ulceration at the week 26 ileocolonoscopy in a patient who had evidence of ulceration at the baseline ileocolonoscopy. RESULTS: 188 patients who had evaluable ileocolonoscopy with evidence of mucosal ulceration at baseline, CDAI scores and CRP values at baseline and week 26 were analysed. Seventy-two of 136 patients (53%) who had a CDAI<150 at week 26 achieved mucosal healing, and 38 of 90 patients (42%) achieved both CRP normalisation (CRP<0.8 mg/dL) and mucosal healing while in clinical remission. The positive predictive value (PPV) and negative predictive value (NPV) of CDAI to detect mucosal healing using 150 as a cut-off for CDAI were 65% and 53%, respectively. The PPV and NPV of CDAI to detect mucosal healing and CRP normalisation using 150 as a cut-off for CDAI were 79% and 42%, respectively. CONCLUSIONS: Half the patients under azathioprine and/or infliximab in clinical remission have endoscopic and/or CRP evidence of residual active CD, whereas other patients with endoscopic and CRP normalisation have persistent clinical symptoms. Clinical symptoms as scored by CDAI are not a reliable measure of the underlying inflammation.

Understanding medication recycling practices in Canadian hospitals.

BACKGROUND: Medication recycling within hospitals has proven financial and possible environmental benefits according to local evaluations done in British Columbia. Despite this, the extent of medication recycling in Canadian hospitals remains unclear in the literature. OBJECTIVE(S): To determine if Canadian hospitals recycle medications, provide an estimate of how much medication is recycled by dosage form, and identify medication recycling barriers through the distribution of a cross-sectional survey. METHODS: A nine-question survey was distributed to 171 hospital pharmacy departments across Canada that consented to complete the survey. The survey identified whether sites recycled unused medications, an estimate of how much is recycled based on dosage form, and barriers to recycling. KEY FINDINGS: Of 62 respondents, the majority indicated they do have medication recycling procedures; however, the frequency of recycling is suboptimal (30-50% of medications are not recycled), and not all medication types are always recycled. Individually packaged oral tablets were most often recycled, and oral liquid medications were least often recycled. Many multi-dose medications were not tamper-proofed. Most respondents selected "sanitization/infection control" and "resource constraint" as reasons for not recycling all medications. CONCLUSIONS: Among respondents, the proportion and type of unused medicines that are recycled varied. For sites that did not respond, this might suggest that medication recycling is not a priority. This could represent a missed opportunity to standardize practices and increase medication recycling in hospitals, both of which could represent a meaningful step towards responsible use of medications and reduction of negative impacts on human health and the environment.

Development and preliminary testing of Health Equity Across the AI Lifecycle (HEAAL): A framework for healthcare delivery organizations to mitigate the risk of AI solutions worsening health inequities.

The use of data-driven technologies such as Artificial Intelligence (AI) and Machine Learning (ML) is growing in healthcare. However, the proliferation of healthcare AI tools has outpaced regulatory frameworks, accountability measures, and governance standards to ensure safe, effective, and equitable use. To address these gaps and tackle a common challenge faced by healthcare delivery organizations, a case-based workshop was organized, and a framework was developed to evaluate the potential impact of implementing an AI solution on health equity. The Health Equity Across the AI Lifecycle (HEAAL) is co-designed with extensive engagement of clinical, operational, technical, and regulatory leaders across healthcare delivery organizations and ecosystem partners in the US. It assesses 5 equity assessment domains-accountability, fairness, fitness for purpose, reliability and validity, and transparency-across the span of eight key decision points in the AI adoption lifecycle. It is a process-oriented framework containing 37 step-by-step procedures for evaluating an existing AI solution and 34 procedures for evaluating a new AI solution in total. Within each procedure, it identifies relevant key stakeholders and data sources used to conduct the procedure. HEAAL guides how healthcare delivery organizations may mitigate the potential risk of AI solutions worsening health inequities. It also informs how much resources and support are required to assess the potential impact of AI solutions on health inequities.

Recycling unused medications in hospitals is financially viable and good for the environment.

OBJECTIVES: Considerable pharmaceutical waste is generated in hospital settings which can be reduced by recycling of unused medications. We sought to determine the recycling practices as well as quantify the volume and the value of oral solid medications returned from nursing units to the pharmacy departments at three urban hospitals. METHODS: Unused oral solid medications were recycled at three sites and the net financial impact of this practice was calculated (cost recovered - labour costs). The results were extrapolated to all 21 hospitals within the health system. KEY FINDINGS: Recycling medications in 21 hospitals could divert ~461 000 units of medication from the incinerator, with an estimated net value of ~$415 000 per year. CONCLUSIONS: Recycling unused medications could save substantial amounts of money and reduce negative environmental impacts from disposal/incineration.

Contraceptive Provision to Women With Intellectual and Developmental Disabilities Enrolled in Medicaid.

OBJECTIVE: To compare contraceptive provision to women with and without intellectual and developmental disabilities enrolled in North Carolina Medicaid. METHODS: Our retrospective cohort study used 2019 North Carolina Medicaid claims to identify women aged 15-44 years with and without intellectual and developmental disabilities at risk for pregnancy who were continuously enrolled during 2019 or had Family Planning Medicaid with at least one claim. We calculated the proportion in each cohort who received 1) most or moderately effective contraception, 2) long-acting reversible contraception, 3) short-acting contraception, and 4) individual methods. We classified contraceptive receipt by procedure type and disaggregated across sociodemographic characteristics. Adjusting for age, race, ethnicity, and urban or rural setting, we constructed logistic regression models to estimate most or moderately effective contraceptive provision odds by intellectual and developmental disability status and by level or type of intellectual and developmental disability. We performed subanalyses to estimate co-occurrence of provision and menstrual disorders. RESULTS: Among 9,508 women with intellectual and developmental disabilities and 299,978 without, a significantly smaller proportion with intellectual and developmental disabilities received most or moderately effective contraception (30.1% vs 36.3%, P <.001). With the exception of injectable contraception, this trend was consistent across all measures and remained statistically significant after controlling for race, ethnicity, age, and urban or rural status (adjusted odds ratio 0.75, 95% CI 0.72-0.79; P <.001). Among those who received most or moderately effective contraception, a significantly greater proportion of women with intellectual and developmental disabilities had co-occurring menstrual disorders (31.3% vs 24.3%, P <.001). CONCLUSION: These findings suggest disparities in contraceptive provision and potential differences in clinical indication by intellectual and developmental disability status. Future studies should investigate reasons for and barriers to contraceptive use among women with intellectual and developmental disabilities.

A pooled analysis of infections, malignancy, and mortality in infliximab- and immunomodulator-treated adult patients with inflammatory bowel disease.

OBJECTIVES: The objective of this study was to analyze the safety of long-term infliximab treatment, with/without concomitant immunomodulators, across Crohn's disease (CD) and ulcerative colitis (UC) clinical trials. METHODS: To maximize sample size, we pooled primary safety data across 10 CD or UC trials, including five randomized, controlled trials contributing data from patients who received intravenous infliximab 5 or 10 mg/kg (n=1,713; ±azathioprine) or placebo (n=406; ±azathioprine). Pooled incidences and 95% confidence intervals (CIs) were determined for mortality, infection, and malignancy. Standardized incidence ratios and 95% CIs were also determined for malignancies using the Surveillance, Epidemiology, and End Results database. RESULTS: We observed no increase in infections, serious infections, or malignancy with infliximab vs. placebo in these patients with inflammatory bowel disease (IBD). In patients with UC, but not CD, immunomodulator treatment (vs. treatment without immunomodulator) yielded a higher incidence (95% CI) of infections (120.07 (110.66, 130.08)/100 patient-years (pt-yrs) vs. 92.47 (84.54, 100.94)/100 pt-yrs). Among placebo-treated patients with CD, but not UC, those with immunomodulator use demonstrated a higher incidence (95% CI) of malignancy vs. no immunomodulator treatment (1.84 (0.22, 6.66)/100 pt-yrs vs. 0.00 (0.00, 0.00)/100 pt-yrs). Mortality and infection-related mortality appeared unaffected by infliximab or immunomodulator treatment. CONCLUSIONS: Infliximab treatment of IBD did not appear to affect incidences of infection, mortality, or malignancy. Relative to patients with no immunomodulator use, immunomodulator-treated UC patients demonstrated a higher incidence of infection and immunomodulator-plus-placebo-treated CD patients demonstrated a higher incidence of malignancy.

Utility of fecal and serum anti-Saccharomyces cerevisiae antibodies in the diagnosis of Crohn's disease-like condition of the pouch.

BACKGROUND: Fecal antibodies against bacterial products may directly reflect the interaction between luminal bacteria and mucosal immunity, and assays for these antibodies may be clinically useful in the diagnosis and differential diagnosis of Crohn's disease-like (CDL) condition of the pouch. AIMS: This study aims to evaluate stool and serum anti-Saccharomyces cerevisiae antibodies (ASCA) in normal and diseased pouches, to assess the correlation between ASCA levels and endoscopic disease activity, and to ascertain the diagnostic utility of ASCA for CDL of the pouch. METHODS: One hundred eighty-nine patients with ileal pouches were prospectively enrolled and corresponding serum and pouch aspirate samples were collected. Fecal and serum ASCA levels were measured with enzyme-linked immunosorbent assay in a blinded fashion. Statistical analysis was then conducted using the signed rank test, Spearman correlation coefficients, and analysis of variance. RESULTS: Forty-three patients (22.8 %) had irritable pouch syndrome or normal pouches, 74 (39.2 %) had pouchitis/cuffitis, 52 (27.5 %) had CDL, 9 (4.8 %) had familial adenomatous polyposis, and 11 (5.8 %) had surgical complications of the pouch. Receiver operating characteristic curves to distinguish CDL from other categories of pouch dysfunction had an area under the curve (AUC) of 0.608 for fecal ASCA and an AUC of 0.517 for serum ASCA. Neither fecal nor serum ASCA correlated with endoscopic disease activity scores. There was a significant difference in the mean values of fecal ASCA between inflammatory and fistulizing CDL (0.27 vs. 0.03 ELISA units/ml, P < 0.05). CONCLUSIONS: Fecal ASCA appears to be better than serum ASCA in differentiating CDL from other pouch disorders, although this distinction may be of limited clinical utility.

Genetic analysis of daf-18/PTEN missense mutants for starvation resistance and developmental regulation during Caenorhabditis elegans L1 arrest.

Mutations in the well-known tumor suppressor PTEN are observed in many cancers. PTEN is a dual-specificity phosphatase that harbors lipid and protein-phosphatase activities. The Caenorhabditis elegans PTEN ortholog is daf-18, which has pleiotropic effects on dauer formation, aging, starvation resistance, and development. Function of 3 daf-18 point-mutants, G174E, D137A, and C169S, had previously been investigated using high-copy transgenes in a daf-18 null background. These alleles were generated based on their mammalian counterparts and were treated as though they specifically disrupt lipid or protein-phosphatase activity, or both, respectively. Here, we investigated these alleles using genome editing of endogenous daf-18. We assayed 3 traits relevant to L1 starvation resistance, and we show that each point mutant is essentially as starvation-sensitive as a daf-18 null mutant. Furthermore, we show that G174E and D137A do not complement each other, suggesting overlapping effects on lipid and protein-phosphatase activity. We also show that each allele has strong effects on nucleocytoplasmic localization of DAF-16/FoxO and dauer formation, both of which are regulated by PI3K signaling, similar to a daf-18 null allele. In addition, each allele also disrupts M-cell quiescence during L1 starvation, though D137A has a weaker effect than the other alleles, including the null. Our results confirm that daf-18/PTEN is important for promoting starvation resistance and developmental arrest and that it is a potent regulator of PI3K signaling, and they highlight challenges of using genetic analysis to link specific DAF-18/PTEN enzymatic activities to particular phenotypes.

Aging reduces liver resiliency by dysregulating Hedgehog signaling.

Older age is a major risk factor for damage to many tissues, including liver. Aging undermines resiliency and impairs liver regeneration. The mechanisms whereby aging reduces resiliency are poorly understood. Hedgehog is a signaling pathway with critical mitogenic and morphogenic functions during development. Recent studies indicate that Hedgehog regulates metabolic homeostasis in adult liver. The present study evaluates the hypothesis that Hedgehog signaling becomes dysregulated in hepatocytes during aging, resulting in decreased resiliency and therefore, impaired regeneration and enhanced vulnerability to damage. Partial hepatectomy (PH) was performed on young and old wild-type mice and Smoothened (Smo)-floxed mice treated with viral vectors to conditionally delete Smo and disrupt Hedgehog signaling specifically in hepatocytes. Changes in signaling were correlated with changes in regenerative responses and compared among groups. Old livers had fewer hepatocytes proliferating after PH. RNA sequencing identified Hedgehog as a top downregulated pathway in old hepatocytes before and after the regenerative challenge. Deleting Smo in young hepatocytes before PH prevented Hedgehog pathway activation after PH and inhibited regeneration. Gene Ontogeny analysis demonstrated that both old and Smo-deleted young hepatocytes had activation of pathways involved in innate immune responses and suppression of several signaling pathways that control liver growth and metabolism. Hedgehog inhibition promoted telomere shortening and mitochondrial dysfunction in hepatocytes, consequences of aging that promote inflammation and impair tissue growth and metabolic homeostasis. Hedgehog signaling is dysregulated in old hepatocytes. This accelerates aging, resulting in decreased resiliency and therefore, impaired liver regeneration and enhanced vulnerability to damage.

Renal allograft compartment syndrome: a review.

Renal allograft compartment syndrome (RACS) is the result of extrinsic compression resulting in graft dysfunction and loss due to ischaemia. A literature review was performed by computerized searches from the following data sources Medline, EMBASE, PubMed and Cochrane Library databases. Risk factors include size mismatch between graft and recipient. Intraoperative suspicion should be exercised if there is poor tissue turgor, cyanosis and loss of urine output upon fascial closure. Doppler ultrasound is the modality of choice amongst the literature to aid in diagnosis of RACS. From our study, the accepted form of treatment is early detection and appropriate surgical intervention. Nevertheless, it is clear from the paucity of literature that further investigation into this area of transplantation is necessary.

How to repair a donor renal vein injury with an inferior vena cava patch.

Shortage of supply of organs for donation means that every viable organ should be given the best chance possible for transplantation. As such, we present a method of renal vein reconstruction of a deceased donor kidney following injury during the organ recovery process.

Hepatocyte activity of the cholesterol sensor smoothened regulates cholesterol and bile acid homeostasis in mice.

Cellular cholesterol is regulated by at least two transcriptional mechanisms involving sterol-regulatory-element-binding proteins (SREBPs) and liver X receptors (LXRs). Although SREBP and LXR pathways are the predominant mechanisms that sense cholesterol in the endoplasmic reticulum and nucleus to alter sterol-regulated gene expression, evidence suggests cholesterol in plasma membrane can be sensed by proteins in the Hedgehog (Hh) pathway which regulate organ self-renewal and are a morphogenic driver during embryonic development. Cholesterol interacts with the G-protein-coupled receptor Smoothened (Smo), which impacts downstream Hh signaling. Although evidence suggests cholesterol influences Hh signaling, it is not known whether Smo-dependent sterol sensing impacts cholesterol homeostasis in vivo. We examined dietary-cholesterol-induced reorganization of whole-body sterol and bile acid (BA) homeostasis in adult mice with inducible hepatocyte-specific Smo deletion. These studies demonstrate Smo in hepatocytes plays a regulatory role in sensing and feedback regulation of cholesterol balance driven by excess dietary cholesterol.

Anesthesia and COVID-19: What We Should Know and What We Should Do.

Coronavirus disease 2019 (COVID-19), caused by Severe Acute Respiratory Syndrome-Coronavirus-2 (SARS-CoV-2), was first reported in Wuhan, Hubei, China, and has spread to more than 200 other countries around the world. COVID-19 is a highly contagious disease with continuous human-to-human transmission. The origin of the virus is unknown. Airway manipulations and intubations, which are common during anesthesia procedures may increasingly expose anesthesia providers and intensive care unit team members to SARS-CoV-2. Through a comprehensive review of existing studies on COVID-19, this article presents the epidemiological and clinical characteristics of COVID-19, reviews current medical management, and suggests ways to improve the safety of anesthetic procedures. Owing to the highly contagious nature of the virus and the lack of therapeutic drugs or vaccines, precautions should be taken to prevent medical staff from COVID-19.

Burnett's "Cocaine" for dandruff.

Joseph Burnett manufactured the diethyl ether used for William T.G. Morton's public demonstration of inhaled surgical anesthesia on October 16, 1846 (Ether Day). A later Burnett product was a hairdressing oil claimed to prevent baldness and dandruff. It contained cocoa-nut oil and was called Cocoaine. In 1902 and 1903, it was sometimes advertised as Burnett's Cocaine (rather than Cocoaine), possibly to emulate the economic success of coca-based beverages such as Vin Mariani and Coca-Cola. Coca leaves are now decocainized before use in preparation of Coca-Cola, and the recovered cocaine is used for scientific and dwindling medical purposes.

Accuracy of estimation of polyp size at colonoscopy.

BACKGROUND: The Cancer Council posits that the size of adenomas is a more robust marker of risk than histological characteristics. The purpose of our study is to assess the accuracy of estimation of polyp size at colonoscopy amongst different levels of endoscopists and compare this with histopathological size. METHODS: A retrospective review of prospectively collected data was performed. Specimens were included if they were (i) from patients aged 18 years or older, (ii) polyp obtained at colonoscopy, (iii) measured in quantitative units and (iv) the largest eligible polyp per patient. RESULTS: A total of 92 patients were included. Our results demonstrate that the relationship between the histological size of a polyp and an endoscopist's estimate depended upon seniority level (P = 0.001). Senior consultants tended to overestimate lesion size (P < 0.001), fellows/junior consultants tended to underestimate size (P = 0.010), whilst registrars' estimates demonstrated no systematic difference from histological size (P = 0.518). The ratio of a senior consultant's estimate of polyp size to histological size was on average 74% with their estimates ranging from 31% to 173%. The corresponding estimates are 123% (32-470%) for fellows/junior consultants and 107% (35-334%) for registrars. CONCLUSION: Our study demonstrates that senior consultants are more precise with more junior endoscopists having a great degree of variability in their practice. It is evident that there is a relationship between proceduralist experience and polyp size estimation. It is, therefore, important to consider the ways in which we can mitigate this learning curve and continue to develop technology to improve our accuracy.

Kety-Schmidt Application of Nitrous Oxide to Determine Cerebral Blood Flow.

In the 1940s, Seymour S. Kety and Carl F. Schmidt measured cerebral blood flow in awake humans by means of subanesthetic doses of inhaled nitrous oxide. The inhalation route obviated the need for an arterial injection of the indicator, and nitrous oxide had virtues of metabolic inertness, rapid diffusion through the blood-brain barrier, comparable blood and brain solubility, and ease of analytical detection. The technique was also applied to the heart. Follow-up work by Kety contributed to the development of brain scanning methods.

Production and evaluation of biosynthesized cellulose tubes as promising nerve guides for spinal cord injury treatment.

Spinal cord injury (SCI) is a central nervous disorder that can result in permanent motor and sensory damage due to a severed communication pathway. Although there is currently no effective treatment, nerve guide tubes have been used to bridge the injured stumps and act as drug delivery systems. In this study, biosynthesized cellulose (BC) nerve guides were prepared, and nerve growth factor (NGF)-a model growth factor-was incorporated into the tubular nerve guide in order to obtain a nerve guide/drug delivery system to assist the regeneration. To achieve this, Gluconacetobacter hansenii was cultivated in a special bioreactor to produce biosynthesized cellulose tubes (BCTs) in situ, and the physical and mechanical properties of the BCTs obtained from different cultivation time points were evaluated. Our results showed that the properties of the BCTs were comparable to those of the native human neural tissues, and that the NGF released from the BCTs was bioactive for at least 7 days as evaluated by PC12 cell cultures in vitro. In summary, this study evaluated the use of BCT as a drug releasing nerve guide, and our results showed that the BCT is an attractive strategy to enhance nerve regeneration after the SCI.