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PURPOSE: Surgical correction of neuromuscular scoliosis is often a challenging and extensive procedure. Due to this complexity and the high disease burden that these patients carry, per and post-operative complications are not uncommon. The purpose of this study was to systematically review and describe the pooled rates of postoperative complications and analyze risk factors for complications in neuromuscular scoliosis surgery described in the literature in the last ten years. METHODS: A systematic review of the English literature across multiple databases was conducted using search criteria (neuromuscular scoliosis AND complications) and using PRISMA guidelines (Jan 2012-July 2022). Studies with less than 30 patients and follow-up of < 2 years were excluded. Data extraction and meta-analysis were performed using random mode effect. Statistical analysis was conducted using OpenMeta software. Meta-regression analysis was used to detect risk factors (surgical approach, intraoperative time, intraoperative blood loss, preoperative Cobb angle and patient diagnosis) associated with each complication group. Confidence interval (CI) was set at 95%. RESULTS: Twenty-two studies met the inclusion criteria involving 2155 patients. The level of evidence among studies were III (9) and IV (13). The most common primary diagnosis was cerebral palsy (43%) followed by Duchenne muscle dystrophy (20%), myelomeningocele (7.4%), spinal muscle atrophy (7.1%), Rett syndrome (< 2%) and combined other pathologies (20.2%). The pooled incidence rate of wound complications was the highest, amongst all complications, at 13.3% (CI 10.838 to 16.861); closely followed by respiratory complications (11.8%;CI 5.7 to 19.7). Implant failure occurred in 7.1% cases (CI 6.418 to 11.465), gastrointestinal complications was 5.2%; CI 2.4 to 8), pseudarthrosis in (4.6%;CI 2.2 to 6.9) and neurological deficit in 2.9% (CI 1.989 to 6.086). The pooled rate of revision surgery was (9.6%; CI 6.2 to 12.9). Heterogeneity was assessed using I2 test which results were moderately heterogeneous. Meta-regression analysis revealed that the diagnosis of myelomeningocele or Duchenne muscle dystrophy or spinal muscle atrophy were strongly associated with wound and respiratory complications (p = 0.007 and p = 0.005, respectively). CONCLUSION: Wound-related (13.3%) and respiratory complications (11.8%) remain the most common complications among studies after corrective surgery for neuromuscular scoliosis. Both are significantly associated with Duchenne muscle dystrophy, spinal muscle atrophy and myelomeningocele.

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STUDY DESIGN: This is a retrospective comparative cohort study. PURPOSE: This study aims to compare the effects of minimally invasive surgery (MIS) and open surgery (OS) on global sagittal alignment (GSA) in surgically managed thoracolumbar fractures. OVERVIEW OF LITERATURE: The optimal treatment of traumatic thoracolumbar fractures (TLF) remains controversial. Both MIS techniques with polyaxial screws and OS techniques with Schanz screws have gained widespread use. The effect of each technique on the global sagittal alignment has not been reported. METHODS: From 2014 to 2021, 22 patients with traumatic TLF underwent open posterior stabilization using an open transpedicular Schanz screw-rod construct and were compared to 15 patients who underwent minimally invasive surgery using a polyaxial percutaneous pedicle screw-rod construct. The reported radiological parameters measured on preoperative supine CT scan and immediate postop standing X-ray and on final follow-up whole spine standing X-rays included pelvic incidence (PI), pelvic tilt (PT), lumbar lordosis (LL), preoperative segmental kyphosis (Preop-K), immediate post-operative segmental kyphosis (postop-Ki), final post-operative segmental kyphosis (postop-Kf), sagittal-vertica-axis (SVA), and spino-sacral angle (SSA). RESULTS: The average age of the OS group was 42.5 years; 5 patients had AO type B, and 17 patients had AO type A (A3 and A4) fractures. The average follow-up was 16.8 months. The average radiological parameters were: PI = 54.9°, PI-LL = 3°, PT = 17.6°, preop-K = 16.2°, postop-Ki = 8.7°, final postop-Kf = 14.3°, SVA = 4.58 cm, and SSA = 101.8°. The average age of the MIS group was 43.4 years; 5 patients had AO type B, and 10 patients had AO type A fractures. The average follow-up was 25 months. The average radiological parameters were as follows: PI = 51°, PI-LL = 8°, PT = 18°, preop-K = 18.4°, postop-Ki = 11.6°, postop-Kf = 14.3°, SVA = 6.4 cm, SSA = 106°. CONCLUSION: The fixation technique did not significantly affect the final correction of the local kyphosis and global spine alignment parameters.

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Background Lateral recess decompression has remained a cornerstone spinal procedure for decades. Despite its popularity, a significant lack of evidence in the literature exists concerning microsurgical anatomy and pertinent surgical landmarks, resulting in non-standardized nomenclature, descriptions, and surgical approaches. Objective This study provides an in-depth microsurgical and descriptive analysis of the subarticular trigone (SAT), serving as an anatomical guide and a tool to foster consistency in nomenclature and standardization of surgical approaches. Methods We analyzed 35 high-resolution lumbar spine CT scans, employing three-dimensional (3D) processing techniques. The SAT is introduced to delineate the bony prominence enveloping the superiomedial quadrant of the pedicle. The SAT encompasses two zones: (1) a superior zone above the superior pedicular line, corresponding to the medial part of the body of the ascending facet (AF), and (2) an inferior zone between the superior and middle pedicular lines, corresponding to the root of the AF and the medial pars/superior lamina. The superior subarticular point (SSP) and medial subarticular point (MESP) serve as key reference landmarks. The SAT forms the roof of the lateral recess and the region requiring resection during decompression of the traversing root in this anatomical corridor. Various measurements, including SSP and MESP to lateral pars, tip of the facet and spino-laminar junction distance, mean width of the sublaminar ridge (SLR), and percentage of the facet that requires resection for adequate SAT decompression, were carried out. Results The mean distance of the SSP to the lateral pars ranges from 7 to 9.2 mm, to the tip of the descending from 9.3 to 10.1 mm, and to the spino-laminar junction from 6.7 to 8.1 mm. The MESP is located at a mean distance of 5.4-6.9 mm from the medial pedicular line. The mean width of the SLR varies from 18.6 to 29.4 mm. Finally, the percentage of total facet width that needs to be removed to adequately decompress the SAT extends from 32% at L4 to 36% at L1. Conclusions This study presents comprehensive insights into the surgical, descriptive, and correlative anatomy of the lateral recess, emphasizing the SAT. The extrapolated data offer a framework for achieving uniformity in surgical planning and advocate for standardized nomenclature.

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Β-arrestins are intracellular scaffolding proteins that have multifaceted roles in different types of disorders. In this review article, we gave a summary about the discovery, characterization and classification of these proteins and their intracellular functions. Moreover, this review article focused on the hepatic expression of ß-arrestins and their hepatocellular distribution and function in each liver cell type. Also, we showed that ß-arrestins are key regulators of distinct types of hepatic disorders. On the other hand, we addressed some important points that have never been studied before regarding the role of ß-arrestins in certain types of hepatic disorders which needs more research efforts to cover.

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BACKGROUND: Malignant spinal cord compression (MSCC) has been noted in 3-5% of children with primary tumours. MSCC can be associated with permanent neurological deficits and prompt treatment is necessary. Our aim was to perform a systematic review on MSCC in children < 18 years to help formulate national guidelines. METHODS: A systematic review of the English language was undertaken using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Search criteria included 'MSCC in children, paediatric and metastases' for papers published between January1999 and December 2022. Isolated case reports/case series with < 10 patients were excluded. RESULTS: From a total of 17 articles identified, a final 7 were analysed (Level III/IV). Neuroblastoma constituted the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%). Soft tissue sarcomas were the most frequent cause of MSCC in children > 5 years old, while for neuroblastomas, the mean age of presentation was 20 months. The median age at time of diagnosis for the entire cohort of patients was 50.9 months (14.8-139). The median follow-up duration was 50.7 months (0.5-204). Motor deficits were the presenting symptom in 95.6% of children followed by pain in 65.4% and sphincter disturbance in 24%. There was a delay of about 26.05 days (7-600) between the onset of symptoms and diagnosis. A multimodality approach to treatment was utilised depending on the primary tumour. The prognosis for neurological recovery was found to be inversely proportional to the degree of neurological deficits and duration of symptoms in four studies. CONCLUSION: Neuroblastoma is the most common cause for MSCC in children (62.7%) followed by sarcoma (14.2%), whilst soft tissue sarcomas constituted the most frequent cause of MSCC in children > 5 years old. The majority of patients presented with motor deficit, followed by pain. In children with neuroblastoma /lymphoma, chemotherapy was the primary treatment. Early surgery should be a consideration with rapid deterioration of neurology despite chemotherapy. A multimodality approach including chemo-radiotherapy and surgery should be the treatment of choice in metastatic sarcomas. It is worth noting that multi-level laminectomy/decompression and asymmetrical radiation to the spine can lead to spinal column deformity in the future.

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Patients with multiple sclerosis (MS) typically experience varying degrees of impairments and disabilities. Task-oriented training (TOT) has been used for those patients to improve their motor skills. This review aimed to evaluate the primary research on the effectiveness of TOT in improving upper limb functions in patients with MS. The systematic search was performed using PubMed, Cochrane library and Physical therapy Evidence Database (PEDro) databases up to 2022. Only randomized controlled trials that used TOT alone for UL functions of adult patients with MS were included. Two independent reviewers screened records, extracted data and assessed studies' quality by using PEDro scale. The meta-analysis was based on the standardized mean differences and the random effect. The search screened 9148 records; only five randomized controlled trials were eligible; four of them were of good quality. The trials included 147 patients with MS; 66% of them were females, their mean average age was 47 years. TOT duration ranged from 40 to 210 min with total period of 10 days to 8 weeks; it was applied alone without conventional physical therapy. Meta-analyses compared TOT alone versus control interventions revealed non-significant difference in the improvement of UL functions on Nine-Hole Peg Test, Action Reach Arm Test, Motor Activity Log-Amount Of Use scale, and Manual Ability Measurement. This review concluded that TOT alone can be effective for improving UL functions in patients with MS but meta-analyses showed non-significant differences when it was compared with conventional physical therapy.

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BACKGROUND: An incidental durotomy (IDT) is a frequent complication of spinal surgery. The conventional management involving a period of flat bed rest is highly debatable. Indeed, there are scanty data and no consensus regarding the need or ideal duration of post-operative bed rest following IDT. OBJECTIVE: To systematically evaluate the literature regarding the outcomes of mobilization within 24 h and after 24 h following IDT in open lumbar or thoracic surgery with respect to the length of hospital stay, minor and major complications. METHODS: A systematic review of the literature using PubMed, Embase and Cochrane and dating up until September 2022 was undertaken following Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines. Quality of evidence was assessed using a modified version of Sackett's Criteria of Evidence Support. RESULTS: Out of 532 articles, 6 studies met the inclusion criteria (1 Level-I, 4 level-III and 1 Level-IV evidence) and were analyzed. Overall, 398 patients of mean age 59.9 years were mobilized within 24 h. The average length of stay (LOS) for this group was 5.7 days. Thirty-four patients (8.5%) required reoperation while the rate of minor complications was 25.4%. Additionally, 265 patients of mean age 63 years with IDT were mobilized after 24 h. The average LOS was 7.8 days. Twenty patients (7.54%) required reoperation while the rate of minor complications was 55%. Meta-analysis comparing early to late mobilization, showed a significant reduction in the risk of minor complications and shorter overall LOS due to early mobilization, but no significant difference in major complications and reoperation rates. CONCLUSIONS: Although early mobilization after repaired incidental dural tears in open lumbar and thoracic spinal surgery has a similar major complication/ reoperation rates compared to late mobilization, it significantly decreases the risk of minor complications and length of hospitalization.

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Dipeptidyl peptidase 4 (DPP4) inhibitors are a class of antidiabetic medications that cause glucose-dependent increase in incretins in diabetic patients. One of the two incretins, glucagon-like peptide-1 (GLP-1), beside its insulinotropic activity, has been studied for extra pancreatic effects. Most of DPP4 inhibitors (DPP4i) have been investigated in in vivo and in vitro models of diabetic and nondiabetic cardiovascular diseases including heart failure, hypertension, myocardial ischemia or infarction, atherosclerosis, and stroke. Results of preclinical studies proved prominent therapeutic potential of DPP4i in cardiovascular diseases, regardless the presence of diabetes. This review aims to present an updated summary of the cardiovascular protective and therapeutic effects of DPP4 inhibitors through the past 5 years focusing on the molecular mechanisms beneath these effects. Additionally, based on the results summary presented here, future studies may be conducted to elucidate or illustrate some of these findings which can add clinical benefits towards management of diabetic cardiovascular complications.

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A new sorbent cetylpyridinium bromide/polyvinylchloride (CPB/PVC) was prepared and tested to extract rare earth elements (REEs) from their chloride solutions. It was identified by FTIR, TGA, SEM, EDX, and XRD. The impact of various factors such as pH, RE ion initial concentration, contacting time, and dose amount via sorption process was inspected. The optimum pH was 6.0, and the equilibrium contact time was reached at 60 min at 25 °C. The prepared adsorbent (CPB/PVC) uptake capacity was 182.6 mg/g. The adsorption of RE ions onto the CPB/PVC sorbent was found to fit the Langmuir isotherm as well as pseudo-second-order models well. In addition, the thermodynamic parameters of RE ion sorption were found to be exothermic and spontaneous. The desorption of RE ions from the loaded CPB/PVC sorbent was investigated. It was observed that the optimum desorption was achieved at 1.0 M HCl for 60 min contact time at ambient room temperature and a 1:60 solid: liquid phase ratio (S:L). As a result, the prepared CPB/PVC sorbent was recognized as a competitor sorbent for REEs.

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This study presents the first application of sodium diethyldithiocarbamate/polyvinyl chloride (DdTC/PVC) as a novel adsorbent for rare earth element (REE) sorption from leach liquors. DdTC/PVC has higher adsorption properties than other sorbents, the synthesis of DdTC/PVC is more accessible than other resins, and it is considered a more affordable sorbent. The three-liquid-phase extraction technique (TLPE) was applied to separate REEs into light, middle, and heavy rare earth elements as groups. The TLPE is an excellent achievable technique in the separation of REEs. DdTC/PVC was prepared as a sorbent to sorb rare-earth ions in chloride solution. It was described by XRD, SEM, TGA, and FTIR. The factors pH, initial rare-earth ion concentration, contact time, and DdTC/PVC dose were also analyzed. The ideal pH was 5.5, and the ideal equilibration time was found to be 45 min. The rare-earth ion uptake on DdTC/PVC was 156.2 mg/g. The rare-earth ion sorption on DdTC/PVC was fitted to Langmuir and pseudo-2nd-order models. The rare-earth ions' thermodynamic adsorption was spontaneous and exothermic. In addition, rare-earth ion desorption from the loaded DdTC/PVC was scrutinized using 1 M HCl, 45 min time of contact, and a 1:60 S:L phase ratio. The obtained rare earth oxalate concentrate was utilized after dissolving it in HCl to extract and separate the RE ions into three groups-light (La, Ce, Nd, and Sm), middle (Gd, Ho, and Er), and heavy (Yb, Lu, and Y)-via three-liquid-phase extraction (TLPE). This technique is simple and suitable for extracting REEs.

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Exosomes (EXOs) were given attention as an extracellular vesicle (EV) with a pivotal pathophysiological role in the development of certain neurodegenerative disorders (NDD), such as Parkinson's and Alzheimer's disease (AD). EXOs have shown the potential to carry pathological and therapeutic cargo; thus, researchers have harnessed EXOs in drug delivery applications. EXOs have shown low immunogenicity as natural drug delivery vehicles, thus ensuring efficient drug delivery without causing significant adverse reactions. Recently, EXOs provided potential drug delivery opportunities in AD and promising future clinical applications with the diagnosis of NDD and were studied for their usefulness in disease detection and prediction prior to the emergence of symptoms. In the future, the microfluidics technique will play an essential role in isolating and detecting EXOs to diagnose AD before the development of advanced symptoms. This review is not reiterative literature but will discuss why EXOs have strong potential in treating AD and how they can be used as a tool to predict and diagnose this disorder.

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The influences of Boswellia serrata resin extract (BSRE) as a feed additive on the growth performance, immune response, antioxidant status, and disease resistance of Nile tilapia, Oreochromis niloticus L. were assessed. One hundred-forty four fingerlings (initial weight: 21.82 ± 0.48 g) were randomly allotted into four groups with three replicates where they were fed on one of four treatments with four levels of Boswellia serrata resin extract 0, 5, 10, or 15 g kg-1, BSRE0, BSRE5, BSRE10, BSRE15, respectively for eight weeks. After the end of the feeding trial, the fish were challenged with Staphylococcus aureus, and mortalities were noted. The final body weight, total body weight gain, and the total feed intake were quadratically increased in BSRE5 treatment (p < 0.01). The protein productive efficiency (PPE) was linearly and quadratically increased in all BSRE supplemented treatments (p < 0.01). Dietary addition of BSRE raised the fish crude protein content and reduced the fat content in a level-dependent manner (p < 0.01). The ash content was raised in the BSRE15 group (p < 0.01). Dietary BSRE supplementation decreased the serum levels of glucose, total cholesterol, triglycerides, and nitric oxide. It increased the serum levels of total protein, albumin, total globulins, α1 globulin, α2 globulin, ß globulin, É£ globulin, Catalase, and SOD (superoxide dismutase) activity, GSH (reduced glutathione), lysozyme activity, and MPO (myeloperoxidase) in a level-dependent manner (p < 0.05). The BSRE15 diet increased the serum level of ALT (alanine aminotransferase) and decreased creatinine serum level (p < 0.05). Dietary BSRE supplementation increased the relative percentage of survival % (RPS) of S. aureus challenged fish. The histoarchitecture of the gills and kidney was normal in the BSRE5 treatment and moderately changed in BSRE10 and BSRE15 treatments. The splenic lymphoid elements were more prevalent, and the melano-macrophage centers (MMC) were mild to somewhat activated in BSRE supplemented treatments. Dietary BSRE supplementation improved the intestinal histomorphology. It can be concluded that BSRE addition can enhance the antioxidant activity, immune status, and disease resistance of O. niloticus to S. aureus infection. The level of 5 g kg-1 BSRE can improve fish growth without causing harmful effects on fish health. The highest levels of BSRE are not recommended as they badly affected the histoarchitecture of many vital organs.

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OBJECTIVE: In our technical note, we have presented a technique of cranioplasty for large skull defects. METHODS: A thin-slice computed tomography scan is performed. A model of the skull is constructed using a desktop 3-dimensional printer from the computed tomography scan. The skull model is filled with towels of soft cotton and inserted in a sterile thin plastic bag. The implant is molded intraoperatively on the skull model under sterile conditions. After surgical exposure of the skull defect, the implant is inserted and fixed using miniplates and miniscrews. The technique was used in 6 patients and described in 2 representative cases. RESULTS: The required time and cost are significantly lower than those for other techniques used for preoperative manufacture of implants. No technique-related complications occurred. The radiological and cosmetic results were satisfactory. In the present case series, no early or delayed complications occurred. CONCLUSION: The presented technique is simple, safe, and time- and cost-effective. The technique and results are reproducible.

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Oxidative stress has been implicated in reproductive toxicity induced by antipsychotics (APs). This study aims to further investigate the role of AP-induced oxidative stress in reproductive dysfunction. Thirty adult female albino rats were divided into three groups including a control group (n = 10) receiving distilled water, HAL group (n = 10) receiving haloperidol (HAL) (2 mg/kg/day), and CLZ group (n = 10) receiving clozapine (CLZ) (20 mg/kg/day). After 28 days, the rats were anesthetized, blood was withdrawn from their hearts, and ovaries were removed before they were sacrificed. Serum prolactin concentrations were measured. For each rat, one ovary was used for biochemical studies including mitochondrial complexes I and III activities and oxidative stress markers (lipid peroxidation, super oxide dismutase [SOD], catalase [CAT], and reduced glutathione [GSH]). The other ovary was used for histopathological examination and immunohistochemistry staining for p53 and Ki-67. HAL-treated rats showed significantly (p < 0.001) higher serum prolactin concentrations compared with other groups. HAL significantly inhibited complexes I (p < 0.001) and III activities (p < 0.05), while CLZ inhibited only complex I (p < 0.001). Lipid peroxidation was increased by HAL (p < 0.001) and CLZ (p < 0.01). HAL caused significant (p < 0.001) reductions in SOD, CAT, and GSH. CLZ caused a significant decrease in SOD (p < 0.001) and GSH (p < 0.01) with no effect on CAT. Histopathological studies of CLZ- and HAL-treated ovaries showed features suggestive of hyperprolactinemia and oxidative stress. Ki-67- and P53-immunostained sections were suggestive of disruption of cellular proliferation. These findings support the hypothesis that HAL and CLZ induce reproductive dysfunction through mechanisms involving ovarian mitochondrial dysfunction and oxidative stress.

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Hg and Cd are non-essential toxic heavy metals that bioaccumulate in the tissues of living systems but less is known about their interactions with Eukaryotic lipid bilayers. Microscopy experiments showed that Hg and Cd changed the cell morphology of rabbit erythrocytes while Hg also induced cell rupture. As membranes are one of the first available targets, our study aimed to better understand metal-lipid interactions that could lead to toxic effects. Fluorescence spectroscopy (Laurdan Generalized Polarization) and dynamic light scattering were used to analyze metal-induced changes in membrane fluidity and the size of liposomes composed of Brain (Porcine), Liver (Bovine), Heart (Bovine) and Yeast (S. cerevisiae) lipid extracts. Under physiological chloride and pH levels, Hg irreversibly cleaves plasmalogens resulting in an increase in membrane rigidity. These lipids are enriched in Brain, Heart and Erythrocyte membranes and are important in signalling and the protection against oxidative stress. Interestingly, Hg had a heavily reduced effect on the plasmalogen-free Yeast extract membrane. In contrast, Cd induced rigidity by targeting negatively charged phosphatidic acid, phosphatidylserine, phosphatidylinositol, phosphatidylglycerol and cardiolipin in these extracts. Metal-induced liposome aggregation depended on the proportion of negatively charged lipids/plasmalogen and even the order of metal addition. Our results show that data from model systems correlate with trends observed in complex biological extracts and red blood cells and serve as a predictive tool for analyzing metal-lipid interactions. The determination of the specific lipid targets for Hg and Cd provides new insights how these metals exert toxic effects on cell membranes.

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Upon uptake of Hg and Cd into living systems, possible targets for metal induced toxicity include the membranes surrounding nervous, cardiovascular and renal cells. To further our understanding of the interactions of Hg and Cd with different lipid structures under physiologically relevant chloride and pH conditions (100 mM NaCl pH 7.4), we used fluorescence spectroscopy and dynamic light scattering to monitor changes in membrane fluidity and phase transition and liposome size. The metal effects were studied on zwitterionic, cationic and anionic lipids to elucidate electrostatically driven metal-lipid interactions. The effect of Hg-catalyzed cleavage of the vinyl ether bond in plasmalogens on these aforementioned properties was studied in addition to a thermodynamic characterization of this interaction by Isothermal Titration Calorimetry. The negatively charged Hg-chloride complexes formed under our experimental conditions induce membrane rigidity in membranes containing cationic lipids and plasmalogens while this effect is heavily reduced and entirely absent with zwitterionic and anionic lipids respectively. The KD for the interaction of Hg with plasmalogen containing liposomes was between 4-30 µM. Furthermore, the presence of Cd affected the interaction of Hg with plasmalogen when negatively charged PS was also present. In this case, even the order of the metal addition was important.

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Inorganic mercury and cadmium are becoming increasingly prevalent due to industrial activity and have been linked to cardiovascular disease and diabetes. The binding affinity of Hg, Cd, and their mixtures to biomimetic erythrocyte membranes was investigated by isothermal titration calorimetry in physiologically relevant media (100 mM NaCl, pH 7.4, 37 °C). The thermodynamic parameters were not expressed per mole of lipid but as metals binding to liposomes. To our knowledge, this method is novel and provides a more intuitive approach to understand such interactions. The results demonstrated that Hg interacted with membranes in the following order: PC (phosphatidylcholine) > 85:15 PC/PE (phosphatidylethanolamine) > 85:15 PC/PS (phosphatidylserine), with the binding constants ranging from 10 to 233 M-1. In contrast, Cd interacted most readily with negatively charged PC/PS membranes but not with the remaining systems. Metal mixtures bind less to PC/PE membranes than the individual constituents. The large entropy contribution from these interactions suggests possible water release and/or reorganization upon Hg and Cd binding to membranes. ζ-Potential data indicate that the process may be electrostatically driven. It is imperative to consider the chemical speciation of these metals in the presence of chloride to better understand metal-lipid interactions and their impact on biomembranes.

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The anthropogenic mobilization of mercury and cadmium into the biosphere has led to an increased and ineludible entry of these metals into biological systems. Here we discuss the impact of Hg(II) and Cd(II) on lipid model systems and human erythrocytes from a biophysical perspective. After a brief introduction to their implications on human health, studies that have investigated the effects of Hg(II) and Cd(II) on lipid model systems and human erythrocytes are discussed. In terms of lipids as toxicological target sites, predominantly variations in lipid head groups have been the source of investigation. However, as research in this field progresses, the effects of Hg(II) and Cd(II) on other structural features, such as acyl chain length and unsaturation, and other important lipid components and complex biomimetic lipid mixtures, will require further examinations. This review provides an analysis of what has been learned collectively from the diverse methodologies and experimental conditions used thus far. Consequently, there is a need for more comprehensive and thorough investigations into the effects of Hg(II) and Cd(II) on lipid membranes under consistent experimental conditions such as pH, ionic strength, temperature, and choice of lipid model system.

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The public health consequences that are associated with the low level exposure of various human populations to Cd(2+) and Hg(2+) are incompletely understood. In order to assess if interactions between these inorganic pollutants and erythrocyte biomembranes may contribute to their chronic toxicity, we have used a Langmuir trough to probe the effect of HgCl2 and CdCl2 on the packing and elasticity properties of biomimetic lipid monolayers using different lipid mixtures. These lipid films were deposited at room temperature on a biologically relevant subphase (1mM phosphate, 100mM NaCl at pH 7.4) in the absence and presence of 100µM HgCl2, CdCl2 and 1:1 mixtures thereof. The interactions of heavy metals with the lipids were monitored as changes in the surface pressure (π)-area (A) isotherms. In addition, metal induced changes to the elastic properties of the model systems were analyzed by area and compressibility data of phosphatidylcholine (PC) systems containing 0, 15, 30, 45 and 100% phosphatidylethanolamine (PE) and phosphatidylserine (PS). These mixtures revealed changes in lateral lipid packing as indicated by area expansion as well as enhanced film rigidity. The results demonstrate that both heavy metals affected the various lipid matrices, but metal mixtures showed the strongest impact. Based on these data, the adverse interaction of Hg(2+) and Cd(2+) with lipid bilayer membranes is identified as a feasible mechanism by which these toxic metals exert toxicity in mammalian cells. Interestingly, these metal interactions were found to depend on the lipid composition.

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