Selective Hepatic Insulin Resistance, VLDL Overproduction, and Hypertriglyceridemia

Insulin plays a central role in regulating energy metabolism, including hepatic transport of very low-density lipoprotein (VLDL)-associated triglyceride. Hepatic hypersecretion of VLDL and consequent hypertriglyceridemia leads to lower circulating high-density lipoprotein levels and generation of small dense low-density lipoproteins characteristic of the dyslipidemia commonly observed in metabolic syndrome and type 2 diabetes mellitus. Physiological fluctuations of insulin modulate VLDL secretion, and insulin inhibition of VLDL secretion upon feeding may be the first pathway to become resistant in obesity that leads to VLDL hypersecretion. This review summarizes the role of insulin-related signaling pathways that determine hepatic VLDL production. Disruption in signaling pathways that reduce generation of the second messenger phosphatidylinositide (3,4,5) triphosphate downstream of activated phosphatidylinositide 3-kinase underlies the development of VLDL hypersecretion. As insulin resistance progresses, a number of pathways are altered that further augment VLDL hypersecretion, including hepatic inflammatory pathways. Insulin plays a complex role in regulating glucose metabolism, and it is not surprising that the role of insulin in VLDL and lipid metabolism will prove equally complex.     

High recurrence rates of Basal cell carcinoma after mohs surgery in patients with chronic lymphocytic leukemia

OBJECTIVES: To estimate and compare the recurrence rates of basal cell carcinoma (BCC) after Mohs surgery in patients with chronic lymphocytic leukemia (CLL) and controls and to evaluate differences among histologic subtypes of BCC. DESIGN: Retrospective assessment of clinical histories, postoperative notes, and surgical photographs. SETTING: Tertiary-care institution (Mayo Clinic, Rochester, Minn). PATIENTS: Twenty-four patients with CLL who underwent Mohs surgery for 33 BCCs and 66 controls matched for sex, age, and surgical year who underwent Mohs surgery for BCC of the head and neck from May 1988 through September 1998. RESULTS: Among the 24 patients with CLL who underwent Mohs surgery for 33 BCCs, there were 4 recurrences. The cumulative incidence of recurrence on a per-tumor basis was 3% at 1 year, 12% at 3 years, and 22% at 5 years. Basal cell carcinoma was 14 times more likely to recur in patients with CLL than in controls (P =.02). Overall, there were no significant differences between patients with CLL and controls in preoperative tumor size (median, 1.6 cm vs 1.4 cm; P =.18) and proportion of aggressive histologic subtypes of BCC (58% vs 41%; P =.12). CONCLUSIONS: Recurrence rates of BCC are significantly higher after Mohs surgery in patients with CLL. Overall, patients with CLL do not appear to have significantly larger BCCs or more aggressive histologic subtypes of BCC. In patients with CLL, close surveillance is warranted for recurrence of BCC and a decreased threshold is indicated for subsequent biopsies.     

Increased metastasis and mortality from cutaneous squamous cell carcinoma in patients with chronic lymphocytic leukemia

In patients with chronic lymphocytic leukemia, squamous cell carcinoma behaves aggressively. Our purpose was to compare squamous cell carcinoma metastasis and mortality between patients with chronic lymphocytic leukemia and control subjects. Medical records were assessed retrospectively for 28 patients with chronic lymphocytic leukemia who underwent surgical excision of cutaneous squamous cell carcinoma and for 56 matched control subjects. The rate of metastasis and mortality from cutaneous squamous cell carcinoma were determined on a per-patient basis. Three of 28 patients with chronic lymphocytic leukemia had metastasis and died of metastatic disease. No metastases or deaths occurred among the 56 control subjects. Compared with control subjects, chronic lymphocytic leukemia patients with cutaneous squamous cell carcinoma were more likely to have metastasis (P = .0031) and die of metastasis (P = .0033). No significant association was detected between metastasis and history of chemotherapy administration for chronic lymphocytic leukemia. Among patients with chronic lymphocytic leukemia, surveillance for skin cancer and a decreased threshold for biopsy of suspect lesions are warranted.     

Efficacy of systemic diclofenac sodium on intravitreal concentration

Background

Nonsteroidal anti-inflammatory drugs (NSAIDs), as an alternative, are replacing corticosteroids in ocular inflammatory diseases. Diclofenac has been used mainly topically, and recent focus has been on intravitreal delivery. Both of these methods have been shown to have complications in long-term application.

Purpose

To assess the efficacy of slow release oral diclofenac sodium on intravitreal concentration in experimental model of chemically injured eyes.

Methods

In an experimental double-masked clinical trial, right eyes of 24 albino rabbits were chemically injured by 1 N NaOH. One hour after chemical injury, 10 cc suspension gavage containing 100 mg slow release diclofenac sodium was administered in all cases. 2, 4, 6, 12, 24, 48 h after gavage, vitreous samples were obtained in all cases. Intravitreal concentration of diclofenac sodium was evaluated in all samples using high-performance liquid chromatography (HPLC) method.

Results

Intravitreal diclofenac levels by oral intake were enhanced by the inflammation in all the measurements. In inflamed eyes, diclofenac concentration was ten times more than control eye (2.658 ± 0.344 vs. 0.242 ± 0.0279 and 1.617 ± 0.527 vs. 0.148 ± 0.095; in 2 and 4 h, respectively). After 6 h, diclofenac concentration was statistically different, although it reduced below 1 μg/ml.

Conclusion

Diclofenac is delivered to the inflamed eye more than healthy eye. It seems that by oral diclofenac consumption, it is possible to make a significant intravitreal concentration.

     

Applications of SMILE-extracted lenticules in ophthalmology

AIM: To review recent innovations, challenges, and applications of small incision lenticule extraction (SMILE) extracted lenticule for treating ocular disorders. METHODS: A literature review was performed in the PubMed database, which was last updated on 30 December 2021. There was no limit regarding language. The authors evaluated the reference lists of the collected papers to find any relevant research. RESULTS: Due to the simplicity and accuracy of modern femtosecond lasers and the extensive development of SMILE surgery, many healthy human corneal stromal lenticules were extracted during surgery, motivating some professionals to investigate the SMILE lenticule reusability in different ocular disorders. In addition, new approaches had been developed to preserve, modify, and bioengineer the corneal stroma, leading to the optimal use of discarded byproducts such as lenticules from SMILE surgery. The lenticules can be effectively re-implanted into the autologous or allogenic corneas of human subjects to treat refractive errors, corneal ectasia, and corneal perforation and serve as a patch graft for glaucoma drainage devices with better cosmetic outcomes. CONCLUSION: SMILE-extracted lenticules could be a viable alternative to human donor corneal tissue.     

Metabolic effects of L-citrulline in type 2 diabetes

The prevalence of type 2 diabetes (T2D) is increasing worldwide. Decreased nitric oxide (NO) bioavailability is involved in the pathophysiology of T2D and its complications. L -citrulline (Cit), a precursor of NO production, has been suggested as a novel therapeutic agent for T2D. Available data from human and animal studies indicate that Cit supplementation in T2D increases circulating levels of Cit and L -arginine while decreasing circulating glucose and free fatty acids and improving dyslipidemia. The underlying mechanisms for these beneficial effects of Cit include increased insulin secretion from the pancreatic β cells, increased glucose uptake by the skeletal muscle, as well as increased lipolysis and β-oxidation, and decreased glyceroneogenesis in the adipose tissue. Thus, Cit has antihyperglycemic, antidyslipidemic, and antioxidant effects and has the potential to be used as a new therapeutic agent in the management of T2D. This review summarizes available literature from human and animal studies to explore the effects of Cit on metabolic parameters in T2D. It also discusses the possible mechanisms underlying Cit-induced improved metabolic parameters in T2D.     

Comprehensive pediatric reference intervals for 79 hematology markers in the CALIPER cohort of healthy children and adolescents using the Mindray BC-6800Plus system

Background

Hematological parameters vary significantly throughout growth and development due to physiological processes such as fetal-to-adult erythropoiesis and puberty. Pediatric age- and sex-specific reference intervals (RIs) are thus essential for appropriate clinical decision-making. The current study aimed to establish RIs for both common and novel hematology parameters on the Mindray BC-6800Plus system.

Methods

Six hundred and eighty-seven healthy children and adolescents (30 days to 18 years) were enrolled. Participants were recruited as part of the Canadian Laboratory Initiative on Pediatric Reference Intervals Program upon informed consent or identified from apparently healthy outpatient clinics. Whole blood was collected and assayed for 79 hematology parameters on the BC-6800Plus system (Mindray). Age- and sex-specific RIs were established as per Clinical and Laboratory Standards Institute EP28-A3c guidelines.

Results

Dynamic reference value distributions were observed for several hematology parameters, including erythrocytes, leukocytes, platelets, reticulocytes, and research-use-only markers. Age partitioning was required for 52 parameters, demonstrating changes in infancy and puberty. Sex partitioning was required for 11 erythrocyte parameters (i.e., red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume, mean corpuscular hemoglobin concentration, RBC distribution width coefficient of variation, hemoglobin distribution width, macrocyte count, macrocyte percentage, RBC (optical), and reticulocyte production index). Few parameters had undetectable levels in our healthy cohort (i.e., nucleated RBC count and immature granulocyte count).

Conclusions

The current study completed hematological profiling for 79 parameters on the BC-6800Plus system in a healthy cohort of Canadian children and adolescents. These data emphasize the complex biological patterns of hematology parameters in childhood, particularly at the onset of puberty, and support the need for age- and sex-specific RIs for clinical interpretation.