Incidences and Outcomes of Operatively Treated Interprosthetic Femoral Fractures Compared to Vancouver Type C and Rorabeck Type II Fractures.

BACKGROUND: This case-control study evaluated the incidences and outcomes of interprosthetic femoral fracture (IPFF) (Group I) and performed comparisons with Vancouver type C (Group II) and Rorabeck type II (Group III) periprosthetic femoral fractures (PPFF) occurring at similar anatomic sites. METHODS: A retrospective analysis was performed for all patients who had a previously implanted total hip arthroplasty (THA) and total knee arthroplasty (TKA), who lived in the hospital district and had undergone surgery due to PPFF. A total of 153 PPFFs [Group I (n = 31), Group II (n = 21), and Group III (n = 108)] were included. The annual incidences of PPFFs were summarized per 100,000 individuals. The risks of complications, reoperations, and mortalities were evaluated for all groups. RESULTS: The mean population-based annual incidence was 0.9 per 100,000 person years for Group I, 0.7 per 100,000 person years for Group II, and 3.1 per 100,000 person years for Group III. A total of 25 of 153 (16%) major complications were found and 23 of 153 (13%) cases resulted in a revision surgery. The cumulative incidence of death in Group I was 50.4% at 10 years, in Group II it was 63.8% at 10 years, and in Group III it was 74.9% at 10 years. CONCLUSION: The annual incidence of the IPFF almost doubled while the incidence of Vancouver type C stayed stable and Rorabeck type II incidence increased 5-fold. Most of the major complications occurred in IPFF group, while Rorabeck type II patients had the worst survival.

CB2 agonist mitigates cocaine-induced reinstatement of place preference and modulates the inflammatory response in mice.

Chronic exposure to cocaine is known to have profound effects on the brain, leading to the dysregulation of inflammatory signalling pathways, the activation of microglia, and the manifestation of cognitive and motivational behavioural impairments. The endocannabinoid system has emerged as a potential mediator of cocaine's deleterious effects. In this study, we sought to investigate the therapeutic potential of the cannabinoid CB2 receptor agonist, JWH-133, in mitigating cocaine-induced inflammation and associated motivational behavioural alterations in an in vivo model. Our research uncovered compelling evidence that JWH-133, a selective CB2 receptor agonist, exerts a significant dampening effect on the reinstatement of cocaine-induced conditioned place preference. This effect was accompanied by notable changes in the neurobiological landscape. Specifically, JWH-133 administration was found to upregulate Δ-FOSB expression in the nucleus accumbens (Nac), elevate CX3CL1 levels in both the ventral tegmental area and prefrontal cortex (PFC), and concurrently reduce IL-1ß expression in the PFC and NAc among cocaine-treated animals. These findings highlight the modulatory role of CB2 cannabinoid receptor activation in altering the reward-seeking behaviour induced by cocaine. Moreover, they shed light on the intricate interplay between the endocannabinoid system and cocaine-induced neurobiological changes, paving the way for potential therapeutic interventions targeting CB2 receptors in the context of cocaine addiction and associated behavioural deficits.

Charlson comorbidity index predicts the 10-year survivorship of the operatively treated hip fracture patients.

PURPOSE: The aim of this study was to determine how Charlson comorbidity index (CCI) predicts the 10-year survival of operatively treated hip fracture patients aged ≥ 65 years. METHODS: This retrospective cohort study included all consecutive patients who had a hip fracture and were operatively treated upon in the study period from 01 January 2007 to 31 December 2007 at the university hospital. The clinical patient data were obtained from the medical records, and CCI score was calculated. The CCI predicts the 10-year mortality for a patient who may have a range of 22 comorbid conditions. Cumulative survival and complications were evaluated in terms of gender. RESULTS: A total of 241 hip fractures were studied; of these, 183/241 (76%) were females. A total of 32/241 (15%) complications were found, of which 26/241 (11%) were considered major. Overall, 213/241 (88%) patients died during the 10 years of follow-up. Cumulative survival estimates for females were 13% at 10 years (SE = 0.3, 95% CI 3.8-4.8), and for males, it was 12% at 10 years (SE = 0.5, 95% CI 2.8-4.6) (p = 0.33). CCI was significantly associated with mortality after the hip fracture as patients with CCI scores ≥ 4 were at a 3.1-8.5 times higher risk of death compared to patients with low CCI scores of 2-3 (p < 0.001). CONCLUSION: Complications are common after operatively treated hip fracture. Advanced age, living in a care facility, ASA class 4 and high CCI score ≥ 4 were risk factors of mortality after the operatively treated hip fracture.

Survival and failure analysis of 167 medial opening wedge high tibial osteotomy with a locking titanium plate.

INTRODUCTION: This retrospective study investigated the survival rate and complications of medial opening wedge high tibial osteotomy (MOWHTO) with a precountered titanium locking plate. HYPOTHESIS: Advanced age (≥50years), gender, body mass index (BMI), type of osteotomy cut (monoplanar or biplanar), osteoarthritis (OA) grade, the use of bone grafting or substitution and preoperative hip-knee-ankle (HKA) have impact on MOWHTO survival. MATERIAL AND METHODS: A total of 167 knees (155 patients) were consecutively operated during the study period of 01.01.2006-31.12.2014. The primary outcome measure was survival without a need for revision to total knee arthroplasty (TKA). The secondary outcome was a major adverse event leading to revision surgery. Adverse events and complications were evaluated and radiological analyses were done. Furthermore, risk factors that affected the survival were analysed with the Cox regression model. RESULTS: The mean follow-up time was 7.7 (SD: 2.7, range: 0.9-14.5) years. The Kaplan-Meier estimates for the cumulative survival considering no need for TKA after MOWHTO was 90% at 5years, 78% at 10years and 61% at 14.5years (SE: 0.4, 95% CI: 11.2-12.9). The adverse event rate was 30% and 35% of the patients required a secondary surgery. The Cox regression model did not show that age, gender, weight, osteotomy type, the use of bone grafting or substitution, preoperative HKA angle or OA grade were not risk factors for conversion to arthroplasty. DISCUSSION: MOWHTO with locking plate provides good survival with no need for TKA in 78% of the knee medial OA patients at 10years of cumulative follow-up. However, a high adverse event rate (30%) is expected. Risk factors for conversion to TKA were not found and thereby hypothesis of this study was not proved. LEVEL OF EVIDENCE: VI; Retrospective cohort study.

Long-term follow-up results of medial opening wedge high tibia osteotomy with a pre-countered non-locking steel plate.

INTRODUCTION: This retrospective study investigated the long-term follow-up results of medial opening wedge high tibial osteotomy (MOWHTO) with a pre-countered non-locking steel plate implant (Puddu plate = PP) used for medial knee osteoarthrosis (OA) treatment. MATERIALS AND METHODS: Consecutive 70 MOWHTOs (66 patients) were performed between 01.01.2004 and 31.12.2008 with the mean follow-up time of 11.4 (SD 4.5; range 1.2-16.1) years. The Kaplan-Meier survival analysis was used to evaluate the cumulative survival of the implant in terms of age (< 50 years old and ≥ 50 years old) and gender. Adverse events were studied and Cox regression analysis was used to evaluate risk factors [age, gender, body mass index (BMI), preoperative mechanical axis, severity of OA, use of bone grafting or substitution and undercorrection of mechanical axis from varus to valgus] for revisions. RESULTS: The estimates for the cumulative survival with no need for TKA after MOWHTO were 86% at 5 years, 67% at 10 years and 58% at 16.1 years (SE 0.6, CI 95% 11.1-13.5). A total of 33/70 (47%) adverse events occurred and 38/70 (54%) knees required some revision surgery during the follow-up. Cox regression did not show any statistically significant risk factors for revision. CONCLUSIONS: The PP has feasible MOWHTO results with a cumulative survival of 67% at 10 years with no need for conversion to TKA. Many adverse events occurred and revision rate due to any reason was high. Age or gender did not have statistically significant differences in terms of survival.

Acoustic emissions and kinematic instability of the osteoarthritic knee joint: comparison with radiographic findings.

To evaluate the acoustic emissions (AE) and kinematic instability (KI) of the osteoarthritic (OA) knee joints, and to compare these signals to radiographic findings. Sixty-six female and 43 male participants aged 44-67 were recruited. On radiography, joint-space narrowing, osteophytes and Kellgren-Lawrence (KL) grade were evaluated. Based on radiography, 54 subjects (the study group) were diagnosed with radiographic OA (KL-grade ≥ 2) while the remaining 55 subjects (KL-grade < 2) formed the control group. AE and KI were recorded with a custom-made prototype and compared with radiographic findings using area-under-curve (AUC) and independent T-test. Predictive logistic regression models were constructed using leave-one-out cross validation. In females, the parameters reflecting consistency of the AE patterns during specific tasks, KI, BMI and age had a significant statistical difference between the OA and control groups (p = 0.001-0.036). The selected AE signals, KI, age and BMI were used to construct a predictive model for radiographic OA with AUC of 90.3% (95% CI 83.5-97.2%) which showed a statistical improvement of the reference model based on age and BMI, with AUC of 84.2% (95% CI 74.8-93.6%). In males, the predictive model failed to improve the reference model. AE and KI provide complementary information to detect radiographic knee OA in females.

Acute cannabidiol treatment attenuates ethanol-induced place preference and reduces aggressivity in group-housed male rats.

Alcohol abuse is a widespread cause of aggressive and impulsive behaviors that impact the users as well as their entourage. However, only a few medications are effective. Recently, cannabidiol has been reported to improve mood disorders and recovery from substance abuse, yet the psychopharmacologic effects of cannabidiol in ethanol-induced drug reward and aggressivity remain unexplored. In the present study, we investigated the effects of cannabidiol on ethanol-induced place preference and aggressivity in individually and group-housed male rats using the conditioned place preference test, and intruder evoc aggression test, respectively. The obtained results showed that ethanol significantly increased locomotor activity, induced conditioned place preference in all animals, and, specifically, increased aggressivity in individually housed rats. These behavioural impairments induced by ethanol were associated with decreased glucocorticoid and mineralocorticoid receptors transcription in the prefrontal cortex. Notwithstanding, cannabidiol at a dose of 10 mg/kg significantly inhibited Et-OH-induced place preference in group-housed, but not in individually housed rats, and markedly inhibited the aggressive behaviour. These findings suggest that ethanol-induced behavioural impairments are dependent on the housing condition that may affect corticosterone receptors expression and subsequently the animal responsivity to cannabidiol treatment.

Ultrasonographic Assessment of the Normal Femoral Articular Cartilage of the Knee Joint: Comparison with 3D MRI.

OBJECTIVE: Ultrasonography (US) has a promising role in evaluating the knee joint, but capability to visualize the femoral articular cartilage needs systematic evaluation. We measured the extent of this acoustic window by comparing standardized US images with the corresponding MRI views of the femoral cartilage. DESIGN: Ten healthy volunteers without knee pathology underwent systematic US and MRI evaluation of both knees. The femoral cartilage was assessed on the oblique transverse axial plane with US and with 3D MRI. The acoustic window on US was compared to the corresponding views of the femoral sulcus and both condyles on MRI. The mean imaging coverage of the femoral cartilage and the cartilage thickness measurements on US and MRI were compared. RESULTS: Mean imaging coverage of the cartilage of the medial femoral condyle was 66% (range 54%-80%) and on the lateral femoral condyle 37% (range 25%-51%) compared with MRI. Mean cartilage thickness measurement in the femoral sulcus was 3.17 mm with US and 3.61 mm with MRI (14.0% difference). The corresponding measurements in the medial femoral condyle were 1.95 mm with US and 2.35 mm with MRI (21.0% difference), and in the lateral femoral condyle, they were 2.17 mm and 2.73 mm (25.6% difference), respectively. CONCLUSION: Two-thirds of the articular cartilage of the medial femoral condyle, and one-third in the lateral femoral condyle, can be assessed with US. The cartilage thickness measurements seem to be underestimated by US. These results show promise for the evaluation of the weight-bearing cartilage of the medial femoral condyle with US.

Anterior glenohumeral instability treated with arthroscopic Bankart operation - a retrospective 5-year follow-up study.

BACKGROUND: This retrospective study investigated 5-year results of primary arthroscopic operation for anterior glenohumeral instability (AI) with special interest in patients aged<25 years and gender. HYPOTHESIS: Recurrence of AI is higher in male patients aged<25 years than older patients or females. PATIENTS AND METHODS: Primary arthroscopic Bankart repair was performed between January 2009 and December 2015 on 156 shoulders [154 patients, 104/156 (67%) males]. The mean follow-up was 5.6 (SD 2.1, range 0.4-8.9) years. Outcome measures, including re-dislocation, fear of dislocation, Western Ontario instability index, Subjective shoulder value and pain Numerical rating scale scores, the number of revision surgeries and satisfaction with the result of surgical treatment, were assessed for 130 shoulders [82/130 (63%) males]. AI recurrence was defined as a dislocation or a fear of such. RESULTS: The Kaplan-Meier analysis estimates for the cumulative survival of stable shoulders were 28% at 8.8 years for patients aged<25 years (SE 0.4, CI 95% 5.5-7.2) and 53% at 8.9 years for patients aged ≥25 years (SE 0.2, CI 95% 7.2-8.0; p=0.005). The Kaplan-Meier estimates for the cumulative survival of stable shoulders were 50% at 8.9 years for males (SE 0.3, CI 95% 6.8-7.8) and 37% at 8.6 years for females (SE 0.3, CI 95% 6.5-7.7; p=0.8). Mean time to revision was 2.4 (SD 1.7, range 0.4-5.3) years. DISCUSSION: Recurrence of AI was higher in the patients aged<25 years (p=0.005), but gender was not a risk factor. Re-operation rate due to recurrent AI was 10% in this 5-year follow-up. LEVEL OF EVIDENCE: III; case-control study.

Retrospective Population-Based Cohort Study of Incidence, Complications, and Survival of 202 Operatively Treated Periprosthetic Femoral Fractures.

BACKGROUND: The aim of this study is to investigate the population and primary total hip arthroplasty (THA)-based incidences, fracture types, complications, and survival of operatively treated periprosthetic femoral fracture (PFF). METHODS: This retrospective study reviewed 202 cases of operatively treated PFFs in a study period from January 2004 to December 2016. The Vancouver classification was used to classify PFFs. RESULTS: The incidence of PFF related to 1000 primary THAs per year was 2.7 (standard deviation 1.0, range 0.9-4.5) at a defined hospital district area during the study period. The mean population-based incidence of operatively treated PFFs raised from 1.6 to 4.5 per 100,000 person-years during the study period. The B1-type fracture was the most common fracture type in 71 of 202 (35%) of these PFFs. The cumulative incidence of re-revision was 10.9% at 1 year and 15.6% at 15 years (95% confidence interval [CI] 10.9-21.0). The cumulative incidence for other major complications was 6.4% at 1 year and 9.9% at 15 years (95% CI 5.9-15.0). The cumulative incidence of death after PFF was 7.4% at 1 year and 56.3% at 15 years (95% CI 41.3-68.8) during the follow-up time from January 1, 2004 to December 31, 2019. CONCLUSION: This country-specific study showed a 3-fold increasing trend in the incidence of operatively treated PFFs from 2004 to 2016 per 1000 THAs. The Vancouver type B1 fracture was the most common type. A high number of complications were associated with PFFs and 7.4% of the patients had died within 1 year after PFF surgery.

Health-Related Quality of Life after Hip and Knee Arthroplasty Operations.

BACKGROUND AND OBJECTIVE: The aim of this study was to investigate the health-related quality of life before and after a hip and a knee arthroplasty operation using a 15D instrument and to compare these scores to the Finnish control population 15D scores. METHODS: The pre- and post-operative data of 15D were prospective collected from the patients undergoing total hip arthroplasty or total knee arthroplasty at the Kuopio University Hospital. Post-operative data were collected at 6 and 12 months after the operation. RESULTS: The mean change of the 15D score after hip arthroplasty was +0.062 and after knee arthroplasty, it was +0.033 at the 12-month follow-up (p < 0.001). Total hip arthroplasty patients of all ages reached the control population 15D scores at the 12-month follow-up. Of the total knee arthroplasty patients, only patients aged >75 years and males aged 55-64 years did reach control population 15D scores at the 12-month follow-up. Patients experienced a statistically significant improvement in mobility, vision, sleeping, usual activities, discomfort and symptoms, distress, and vitality (p < 0.05). CONCLUSIONS: Successful hip and knee arthroplasty operations improve patients' health-related quality of life. According to this study, hip arthroplasty improves the health-related quality of life more than knee arthroplasty.

Comparison of ultrasonographic, radiographic and intra-operative findings in severe hip osteoarthritis.

Aim of this study was to assess the US findings of patients with late-stage hip OA undergoing total hip arthroplasty (THA), and to associate the US findings with conventional radiography (CR) and intraoperative findings. Moreover, the inter-rater reliability of hip US, and association between the US and Oxford Hip Score (OHS) were evaluated. Sixty-eight hips were included, and intraoperative findings were available on 48 hips. Mean patient age was 67.6 years and 38% were males. OA findings-osteophytes at femoral collum and anterosuperior acetabulum, femoral head deformity and effusion-were assessed on US, CR and THA. The diagnostic performance of US and CR was compared by applying the THA findings as the gold standard. Osteoarthritic US findings were very common, but no association between the US findings and OHS was observed. The pooled inter-rater reliability (n = 65) varied from moderate to excellent (k = 0.538-0.815). When THA findings were used as the gold standard, US detected femoral collum osteophytes with 95% sensitivity, 0% specificity, 81% accuracy, and 85% positive predictive value. Concerning acetabular osteophytes, the respective values were 96%, 0%, 88% and 91%. For the femoral head deformity, they were 92%, 36%, 38% and 83%, and for the effusion 49%, 85%, 58% and 90%, respectively. US provides similar detection of osteophytes as does CR. On femoral head deformity, performance of the US is superior to CR. The inter-rater reliability of the US evaluation varies from moderate to excellent, and no association between US and OHS was observed in this patient cohort.

Association between grayscale sonographic and clinical findings in severe knee osteoarthritis.

PURPOSE: To assess whether ultrasonographic (US) findings associate with clinical findings in severe knee osteoarthritis (OA). Association of US findings with side-of-knee pain and inter-reader agreement of knee US were also evaluated. METHODS: One-hundred-two patients (in total 123 knees) with severe knee OA were recruited for this cross-sectional study. US was performed by a single observer, and on 53 knees by two independent observers to assess inter-reader reliability. Preoperative clinical data was available for 69 knees. Cutoff values were applied to dichotomize US and clinical findings. The Chi-square test, Mann-Whitney test, and prevalence- and bias-adjusted kappa (PABAK) were applied for statistical analyses. RESULTS: Seven of 99 associations tested were statistically significant. Associations were observed between range of flexion and lateral femoral (P = .009) and tibial (P = .001) osteophytes, mediolateral instability and damage to the lateral femoral cartilage (P = .014) and damage to the lateral meniscus (P = .031), and alignment and damage to the lateral femoral cartilage (P < .001), lateral tibial osteophytes (P = .037), and damage to the lateral meniscus (P < .001). A strong association was observed between medial-sided pain and same-sided cartilage damage and osteophytes (P < .001). That inter-reader agreement was excellent on the medial side of the knee joint (PABAK = 0.811-0.887). CONCLUSIONS: US findings show a rather poor association with clinical OA findings. Inter-reader agreement of knee US is excellent on the medial side.

Signatures of HIV-1 subtype B and C Tat proteins and their effects in the neuropathogenesis of HIV-associated neurocognitive impairments.

HIV-associated neurocognitive impairments (HANI) are a spectrum of neurological disorders due to the effects of HIV-1 on the central nervous system (CNS). The HIV-1 subtypes; HIV-1 subtype B (HIV-1B) and HIV-1 subtype C (HIV-1C) are responsible for the highest prevalence of HANI and HIV infections respectively. The HIV transactivator of transcription (Tat) protein is a major contributor to the neuropathogenesis of HIV. The effects of the Tat protein on cells of the CNS is determined by the subtype-associated amino acid sequence variations. The extent to which the sequence variation between Tat-subtypes contribute to underlying mechanisms and neurological outcomes are not clear. In this review of the literature, we discuss how amino acid variations between HIV-1B Tat (TatB) and HIV-1C Tat (TatC) proteins contribute to the potential underlying neurobiological mechanisms of HANI. Tat-C is considered to be a more effective transactivator, whereas Tat-B may exert increased neurovirulence, including neuronal apoptosis, monocyte infiltration into the brain, (neuro)inflammation, oxidative stress and blood-brain barrier damage. These findings support the premise that Tat variants from different HIV-1 subtypes may direct neurovirulence and neurological outcomes in HANI.

Dislocation of large-diameter head metal-on-metal total hip arthroplasty and hip resurfacing arthroplasty.

INTRODUCTION: Dislocation of large-diameter head (LDH) metal-on-metal (MoM) total hip arthroplasty (THA) or hip resurfacing arthroplasty (HRA) is a rare complication. This study aimed to determine the incidence and risk factors for dislocation of LDH MoM THAs and HRAs. METHODS: This retrospective analysis considered 4038 cementless LDH MoM THAs and HRAs, 3207 THAs in 2912 patients and 831 HRAs in 757 patients. The end of follow-up was revision due to dislocation. Incidence of dislocation was evaluated from this study population of 4038, and study groups were formed. The study was designed as a case-control study, and a threefold stratified randomised control group was formed. Demographic data were collected and radiological analyses were performed in the study groups. RESULTS: There were 26/3207 (0.8%) early dislocations in the THA group, and 6/831 (0.7%) in the HRA group ( p = 0.9). Most LDH THA dislocations occurred in a group with head size ⩽ 38 mm (18/26) ( p < 0.001). In dislocated hips, there were more dysplastic acetabula and post-traumatic hips than in the control group ( p = 0.036). In the dislocation group, the mean acetabulum component anteversion angle was 19.6° (standard deviation [SD] 13.4°) and in the control group it was 23.2° (SD 10.4°) ( p = 0.006); 7/32 (21.8%) of dislocated THAs needed revision surgery, and mean time to revision from the index surgery was 1.2 (SD 2.6) years. DISCUSSION: Dislocations occurred more often in THAs of head size ⩽ 38 mm and with a smaller anteversion angle of the acetabulum component. Hip dysplasia and post-traumatic osteoarthritis were more common in patients with dislocation.

Effect of long-term administration of antiretroviral drugs (Tenofovir and Nevirapine) on neuroinflammation and neuroplasticity in mouse hippocampi.

The use of combination antiretroviral therapy (cART) has been successful in suppressing HIV-1 replication and restoring peripheral immune functioning in HIV-infected individuals. Despite these advances in the management of HIV, neurocognitive impairments continue to be diagnosed in HIV-infected patients on treatment, even when the viral load is low. Of interest is the observation that deficiencies in brain function in these individuals are marked by a persistent presence of neuroinflammation. Therefore, in this study we investigated whether long-term exposure to ART could contribute to neuroinflammation. Mice were subsequently administered a daily single dose of either Tenofovir disoproxil fumarate or Nevirapine orally for 8 weeks. After treatment, hippocampal tissue was collected from the brains of drug-treated and control mice and the levels of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α) and brain-derived neurotrophic factor (BDNF) determined. Our results showed that administration of Tenofovir disoproxil fumarate and Nevirapine induced astrogliosis and up-regulated IL-1ß and TNF-α. In addition, we found that Nevirapine reduced the expression of BDNF. Together these results suggest that Nevirapine promotes inflammatory and reduces neuroprotective processes in the hippocampus of mice. Our findings therefore highlight the potential of ART to be harmful to the brain and as such these drugs may contribute to the development of HIV-associated neurocognitive disorder (HAND).

Significance of Taurine in the Brain.

Two main functions of taurine in the brain are here discussed: the role of taurine in cell volume regulation and the neuromodulatory actions of taurine liberated by depolarization. Taurine takes part in cell volume regulation with other small-molecular compounds. Extracellular taurine inhibits neuronal firing through GABA and glycine receptors. However, the existence of specific taurine receptors is still not excluded.

Comparison of Toxicity of Taurine and GABA in Combination with Alcohol in 7-Day-Old Mice.

Previously, we described the combined toxicity of taurine and alcohol, and assumed hypoglycemia to be one reason of this toxicity. To understand whether taurine-ethanol combined toxicity is exclusively connected to taurine or whether other inhibitory amino acids may have similar effects when combined with ethanol, we tested different doses of gamma-aminobutyric acid (GABA) in combination with ethanol in 7-day-old mice. The minimal dose of GABA in combination with 5 g/kg ethanol which could kill a mouse was 2 g/kg. GABA combined with ethanol at doses of 3 g/kg, 4 g/kg, 6 g/kg induced lethality of 30%, 90% and 100%, correspondingly. Taurine at the doses of 4 and 6 g/kg combined with ethanol induced death in 60 and 100% of mice. Ethanol (5 g/kg), taurine (6 g/kg), GABA (4 g/kg) administered alone and the combination of ethanol (5 g/kg) with taurine (3 g/kg) have no lethal effects. GABA (6 g/kg) applied alone induced 90% lethality. Taurine or GABA alone decreased blood glucose in a dose-depending manner. Ethanol potentiated GABA- and taurine-induced decrease in blood glucose and in some animals it dropped from 8.8 (intact) to a hypoglycemic level 3.1-3.3 mmol/L (GABA 4 g/kg, taurine 6 g/kg), but this may not be considered a single reason of death. We conclude that the combination of GABA and ethanol has a lethal effect and this is stronger than the combined toxicity of ethanol and taurine.

Neurotoxicity of Ammonia.

Abnormal liver function has dramatic effects on brain functions. Hyperammonemia interferes profoundly with brain metabolism, astrocyte volume regulation, and in particular mitochondrial functions. Gene expression in the brain and excitatory and inhibitory neurotransmission circuits are also affected. Experiments with a number of pertinent animal models have revealed several potential mechanisms which could underlie the pathological phenomena occurring in hepatic encephalopathy.