Prone position lateral interbody fusion-a narrative review.

Background and Objective: Lateral access lumbar interbody fusion is an increasingly popular procedure that allows for anterior column support through discectomy, endplate preparation, and interbody insertion. This procedure was initially described and performed with the patient in the lateral decubitus position. This would typically be followed by repositioning the patient to the prone position for pedicle screw fixation. Increasingly common is the lateral access lumbar interbody fusion in the prone position. This narrative review seeks to summarize the available literature on advantages, disadvantages, and unique features of the prone position lateral access lumbar interbody fusion. Methods: We performed a narrative review of articles published up to 01 November 2022 through a PubMed search. The search terms "prone lateral spine surgery" and "lateral approach spine surgery" AND "prone position" were used. Articles not available in English were excluded. The search result abstracts were independently reviewed by 2 authors and 28 full text articles were reviewed. Both reviewing authors were orthopedic surgery chief residents. Key Content and Findings: There are several unique advantages as well as disadvantages to the prone position lateral interbody fusion. Some advantages include ease of placing pedicle screws, simultaneous posterior and lateral access, greater ease in achieving segmental lumbar lordosis, and a relatively safer positioning of the psoas muscle, lumbar plexus, and abdominal structures. Disadvantages include more difficulties with exposure and retraction, as well as visualization, positioning and ergonomics of surgery. Conclusions: Prone position lateral interbody fusion is an increasingly prevalent and useful surgical technique with several advantages and disadvantages when compared to lateral interbody fusion in the lateral decubitus position. There are several surgical indications and goals for which prone lateral interbody fusion may provide significant benefit when compared to other interbody fusion techniques.

Coagonist of glucagon-like peptide-1 and glucagon receptors ameliorates kidney injury in murine models of obesity and diabetes mellitus.

AIM: To investigate the role of glucagon-like peptide-1 (GLP-1)/glucagon receptors coagonist on renal dysfunction associated with diabetes and obesity. METHODS: Chronic high-fat diet fed C57BL/6J mice, streptozotocin-treated high-fat diet fed C57BL/6J mice and diabetic C57BLKS/J db/db mice were used as models of diabetes-induced renal dysfunction. The streptozotocin-treated high-fat diet fed mice and db/db mice were treated with the GLP-1 and glucagon receptors coagonist (Aib2 C24 Chimera2, 150 µg/kg, sc) for twelve weeks, while in chronic high-fat diet fed mice, coagonist (Aib2 C24 Chimera2, 150 µg/kg, sc) treatment was continued for forty weeks. Kidney function, histology, fibrosis, inflammation, and plasma biochemistry were assessed at the end of the treatment. RESULTS: Coagonist treatment decreased body weight, plasma lipids, insulin resistance, creatinine, blood urea nitrogen, urinary albumin excretion rate and renal lipids. In kidney, expression of lipogenic genes (SREBP-1C, FAS, and SCD-1) was decreased, and expression of genes involved in ß-oxidation (CPT-1 and PPAR-α) was increased due to coagonist treatment. In plasma, coagonist treatment increased adiponectin and FGF21 and decreased IL-6 and TNF-α. Coagonist treatment reduced expression of inflammatory (TNF-α, MCP-1, and MMP-9) and pro-fibrotic (TGF-ß, COL1A1, and α-SMA) genes and also improved histological derangement in renal tissue. CONCLUSION: Coagonist of GLP-1 and glucagon receptors alleviated diabetes and obesity-induced renal dysfunction by reducing glucose intolerance, obesity, and hyperlipidemia.

Consequences of daily corticosteroid dosing with or without pre-treatment with quinidine on the in vivo cytochrome P450 2D (CYP2D) enzyme in rats: effect on O-demethylation activity of dextromethorphan and expression levels of CYP2D1 mRNA.

1. Present investigation was carried out in rats to study influence of corticosteroids after repeated dosing with/without pre-treatment with CYP2D inhibitor quinidine on the CYP2D1 mRNA levels and CYP2D enzyme activity using dextromethorphan as probe substrate. 2. CYP2D1 mRNA was measured in liver homogenate using quantitative real-time polymerase chain reaction [qRT-PCR] and enzymatic reaction was studied ex vivo in liver S-9 fractions of rats treated with oral 10 mg/kg dexamethasone or prednisolone for five days or pre-treated with quinidine and followed by treatment with oral 10 mg/kg corticosteroids for five days. 3. Five days repeat dosing of dexamethasone or prednisolone decreased the activity of the rat liver CYP2D by 37% and 34%, at 30 min incubation and decreased CYP2D1 mRNA levels by 62% and 61%, respectively. 4. Pre-treatment of quinidine decreased the enzymatic activity of rat CYP2D by 58% and did not potentiate CYP2D inhibition by corticosteroids. This observation was further complemented by qRT-PCR data. 5. Corticosteroids caused CYP2D inhibition in rats vs. literature evidence of CYP2D induction in human hepatocytes/pregnant humans demonstrating lack of concordance. In vivo inhibition should be factored for interpretation of pharmacokinetic data of CYP2D substrates when treated with corticosteroids in rats.

Balanced Coagonist of GLP-1 and Glucagon Receptors Corrects Dyslipidemia by Improving FGF21 Sensitivity in Hamster Model.

Hyperlipidemia is often associated with obesity and diabetes, and can lead to serious complications like atherosclerosis and fatty liver disease. Coagonist of GLP-1 and glucagon receptors is a therapy under clinical investigation for treatment of obesity and diabetes. In this study, we have characterized the mechanism of hypolipidemic effect of a balanced coagonist using high cholesterol-fed hamsters. Tyloxapol-induced hypertriglyceridemia, lipolysis in adipose tissue, and bile homeostasis were assessed after repeated dose treatment of the coagonist of GLP-1 and glucagon receptors (Aib2 C24 chimera 2, SC). Antagonists of GLP-1, glucagon, and FGF21 receptors were coadministered, and FGF21 sensitivity was determined in liver and adipose tissue. Repeated dose treatment of coagonist reduced cholesterol and increased FGF21 in blood and liver. Coagonist treatment reduced hepatic triglyceride secretion, increased lipolysis and reduced body weight. Antagonism of GLP-1 and glucagon receptors partially blocked the effect of the coagonist on lipid metabolism in circulation and liver, while FGF21 receptor antagonist completely abolished it. Glucagon and GLP-1 receptors antagonists blocked the action of coagonist on cholesterol excretion and bile flow in liver, but FGF21 antagonist was not effective. Treatment with the coagonist increased expression of FGF21, FGF21R and cofactor ßKlotho in liver and adipose. In conclusion, coagonist of GLP-1 and glucagon receptors improved lipid metabolism in liver of dyslipidemic hamsters. This effect is partially mediated by GLP-1 and glucagon receptors, and the improved FGF21 sensitivity could be the mechanism of hypolipidemic action of the coagonist of GLP-1/glucagon receptors.

Central and Peripheral Glucagon Reduces Hyperlipidemia in Rats and Hamsters.

Increased lipid levels in blood contribute to increasing the risk of diabetic complications. Glucagon exerts lipid lowering effects in diabetic state. However, the mechanism behind the lipid reduction by glucagon independent of glucose homeostasis is not well understood. We assessed the actions of glucagon on lipid modulation in blood and markers in liver in hyperlipidemic hamsters and rats. Male Sprague Dawley rats and Golden Syrian hamsters on a hyperlipidemic diet for 2 weeks were administered a single dose of glucagon by subcutaneous (SC, 150 and 300 µg/kg) or intracerebroventricular (ICV, 15 and 30 µg/animal) route. Effect of acute treatment was observed on tyloxapol-induced hypertriglyceridemia, corn oil-induced post-prandial lipemia, and bile flow. A repeated dose treatment by subcutaneous (300 µg/kg) or intracerebroventricular (30 µg/animal) route was done for 2 weeks, following which circulating and hepatic lipids, hepatic markers of lipid metabolism and bile flow were assessed. Acute administration of glucagon (SC and ICV) decreased triglyceride absorption, hepatic triglyceride secretion rate and increased excretion of cholesterol in bile fluid in dose related manner. Repeated dose treatment reduced circulating and hepatic lipids and mainly LDL, and enhanced cholesterol excretion in bile. In liver, expression of HMG-CoA reductase was reduced while that of ABCA1 was increased after repeated treatment, whereas pair fed group did not show significant changes when compared to the control group. These findings demonstrate that central as well as peripheral glucagon effectively reduces hyperlipidemia in rat and hamster model, by modulating hepatic lipid metabolism.

Ameliorative potential of aliskiren in experimental colitis in mice.

In the present study, we investigated the ameliorative potential of aliskiren in dextran sulfate sodium (DSS) induced colitis in mice. Aliskiren (3 and 10mg/kg, i.p.) was administered for 10 days from the day of DSS administration. The severity of colitis in mice was assessed using body weight loss, colon and spleen weight, hematological parameters, food intake, stool consistency, rectal bleeding and colon shortening. Colonic malondialdehyde (MDA), myeloperoxidase (MPO) and renin mRNA levels were also estimated. Furthermore, TNF-α and IL-6 in plasma and colon were analyzed. The results showed that aliskiren (10mg/kg, i.p.) significantly improved the severity of colitis by, decrease in weight loss, improvement in food intake and stool consistency, decrease in rectal bleeding, decrease in relative colon and spleen weight and improvement in colonic shortening. Aliskiren (10mg/kg, i.p.) improved blood hemoglobin, red blood cells (RBC) and hematocrit. Colonic malondialdehyde (MDA), MPO and histolopathological score were significantly diminished by aliskiren (10mg/kg, i.p.). Furthermore, aliskiren (10mg/kg, i.p.) significantly diminished the elevated levels of TNF-α, IL-6 and renin mRNA in inflammed colon. These results indicate involvement of renin in colitis and inhibition of renin by aliskiren ameliorates colitis.

Involvement of TACE in colon inflammation: a novel mechanism of regulation via SIRT-1 activation.

TNF-α converting enzyme (TACE) processes the membrane TNF-α to release the bioactive soluble TNF-α. Several evidences suggest the involvement of TNF-α and TACE in inflammatory bowel disease (IBD). Tissue inhibitor of metalloproteinase (TIMP)-3, an endogenous inhibitor of TACE, is positively associated with silent information regulator (SIRT)-1. We aimed to study the expression of TACE, TIMP-3 and SIRT-1 at different stages of colitis and how TACE is regulated in response to SIRT-1 activation. Acute colitis was induced by 3.5% dextran sulfate sodium (DSS) in drinking water for 5days and levels of cytokines and mRNA expression of TACE, TIMP-3 and SIRT-1 were measured in colon at different time intervals. Next, the effect of SIRT-1 activator (resveratrol) or a selective TACE inhibitor (compound 11p) treatment was evaluated. Elevated levels of TNF-α, interleukin (IL)-6, IL-1ß, interferon (IFN)-γ and IL-17 were observed during DSS exposure phase which restored to the normal level after DSS removal. A significant increase in TACE and suppression in TIMP-3 and SIRT-1 mRNA level was observed during DSS exposure phase which reverts back to normal towards the remission phase. Treatment with resveratrol significantly elevated SIRT-1 and TIMP-3 and suppressed TACE mRNA expression and was associated with amelioration of disease. Furthermore, treatment with selective TACE inhibitor significantly suppressed body weight loss, disease activity index, colonic myeloperoxidase activity and the elevated levels of cytokines after DSS challenge. These results strongly emphasize the involvement of TACE in colon inflammation and inhibition of TACE directly or indirectly via SIRT-1 activation ameliorates colitis.

Selective inhibition of tumor necrosis factor-α converting enzyme attenuates liver toxicity in a murine model of concanavalin A induced auto-immune hepatitis.

Emerging evidence suggest that tumor necrosis factor (TNF)-α plays a major role in pathogenesis of auto-immune hepatitis (AIH) induced liver injury. Blockade of TNF-α synthesis or bio-activity protects against experimental AIH. TNF-α converting enzyme (TACE) is a member of the ADAM (a disintegrin and metalloproteinase) family which processes precursor TNF-α to release soluble TNF-α. We hypothesized that selective inhibition of TACE might protect AIH. To investigate this, we studied the effects of a selective TACE inhibitor DPC-333 on murine model of liver injury and fibrosis induced with concanavalin A (Con A). Pre-treatment with DPC-333 significantly suppressed plasma alanine transaminase, aspartate transaminase and cytokines such as TNF-α, interferon (IFN)-γ, interleukin (IL)-2 and IL-6 levels due to acute Con A challenge. Interestingly; DPC-333 inhibited liver poly (ADP-ribose) polymerase (PARP)-1 activity which was associated with reduced number of necrotic hepatocytes in histological examination and mortality associated with Con A. In fibrosis study, repeated Con A administration significantly up-regulated liver collagen deposition as assessed by measurement of hydroxyproline content which was further confirmed in liver histology with Masson's trichrome staining. Treatment with 30mg/kg of DPC-333 was able to suppress liver hydroxyproline and fibrous tissue proliferation which corroborated well with inhibition in expression of pro-fibrotic genes such as tissue inhibitor of metalloproteinase (TIMP)-1 and transforming growth factor (TGF)-ß1. These observations suggest that selective TACE inhibition is an effective approach for the treatment of both immune mediated hepatic inflammation and fibrosis.