Increased Alkaline Phosphatase Levels Research Articles

Photobiomodulation Dose-Response on Adipose-Derived Stem Cell Osteogenesis in 3D Cultures.

Osteoporosis and other degenerative bone diseases pose significant challenges to global healthcare systems due to their prevalence and impact on quality of life. Current treatments often alleviate symptoms without fully restoring damaged bone tissue, highlighting the need for innovative approaches like stem cell therapy. Adipose-derived mesenchymal stem cells (ADMSCs) are particularly promising due to their accessibility, abundant supply, and strong differentiation potential. However, ADMSCs tend to favor adipogenic pathways, necessitating the use of differentiation inducers (DIs), three-dimensional (3D) hydrogel environments, and photobiomodulation (PBM) to achieve targeted osteogenic differentiation. This study investigated the combined effects of osteogenic DIs, a fast-dextran hydrogel matrix, and PBM at specific wavelengths and fluences on the proliferation and differentiation of immortalized ADMSCs into osteoblasts. Near-infrared (NIR) and green (G) light, as well as their combination, were used with fluences of 3 J/cm2, 5 J/cm2, and 7 J/cm2. The results showed statistically significant increases in alkaline phosphatase levels, a marker of osteogenic differentiation, with G light at 7 J/cm2 demonstrating the most substantial impact on ADMSC differentiation. Calcium deposits, visualized by Alizarin red S staining, appeared as early as 24 h post-treatment in PBM groups, suggesting accelerated osteogenic differentiation. ATP luminescence assays indicated increased proliferation in all experimental groups, particularly with NIR and NIR-G light at 3 J/cm2 and 5 J/cm2. MTT viability and LDH membrane permeability assays confirmed enhanced cell viability and stable cell health, respectively. In conclusion, PBM significantly influences the differentiation and proliferation of hydrogel-embedded immortalized ADMSCs into osteoblast-like cells, with G light at 7 J/cm2 being particularly effective. These findings support the combined use of 3D hydrogel matrices and PBM as a promising approach in regenerative medicine, potentially leading to innovative treatments for degenerative bone diseases.

Obeticholic acid's effect on HDL function in MASH varies by diabetic status.

Inflammation and oxidative stress are the key factors in the pathogenesis of both metabolic dysfunction-associated steatohepatitis (MASH) and atherosclerosis. Obeticholic acid (OCA), a farnesoid X receptor (FXR) agonist, improves hepatic inflammation and fibrosis in patients with MASH. However, it also reduces HDL cholesterol, suggesting that OCA may increase cardiovascular disease (CVD) risk in patients with MASH. We assessed HDL cholesterol efflux function, antioxidant (paraoxonase and ceruloplasmin activity), pro-inflammatory index, and particle sizes in a small group of patients with and without diabetes (n = 10/group) at baseline and after 18 months of OCA treatment. Patients on lipid-lowering medications (statins, fibrates) were excluded. At baseline, ferritin levels were higher in patients with MASH without diabetes (336.5 [157.0, 451.0] vs. 83 [36.0, 151.0] ng/mL, p < 0.005). Markers of HDL functions were similar in both groups. OCA therapy significantly improved liver histology and liver enzymes but increased alkaline phosphatase levels in nondiabetic patients with MASH (p < 0.05). However, it did not have any significant effect on cholesterol efflux and the antioxidant paraoxonase functions. In nondiabetics, ceruloplasmin (CP) antioxidant activity decreased (p < 0.005) and the pro-inflammatory index of HDL increased (p < 0.005) due to OCA therapy. In contrast, in diabetics, OCA increased levels of pre-β-HDL-the HDL particles enhanced protective capacity (p = 0.005) with no alteration in HDL functionality. In all patients, serum glucose levels were negatively correlated with OCA-induced change in pro-inflammatory function in HDL (p < 0.001), which was primarily due to diabetes (p = 0.05). These preliminary results suggest a distinct effect of OCA therapy on diabetic and nondiabetic patients with MASH and warrant a future large-scale study.

Safety and efficacy of burosumab in improving phosphate metabolism, bone health, and quality of life in adolescents with X-linked hypophosphatemic rickets

Background and objectiveX-linked hypophosphatemic rickets (XLH) is due to loss-of-function mutations in the phosphate-regulating endopeptidase homologue on the X chromosome (PHEX) that lead to increased fibroblast growth factor 23 (FGF23) production. FGF23 excess causes renal phosphate wasting and insufficient 1,25-dihydroxyvitamin D (1,25(OH)2D) synthesis with reduced intestinal phosphate absorption, ultimately resulting in chronic hypophosphatemia.Children with XLH show typical skeletal lesions of rickets, deformities of the lower limbs, stunted growth with disproportionate short stature, bone pain, and physical dysfunctions.Burosumab, a fully human IgG1 monoclonal antibody that binds to FGF23 to inhibit its activity, is more effective to improve the biochemical and clinical signs of XLH than conventional treatment with phosphate supplements and vitamin D active metabolites. Data on adolescents with XLH during the transition period to young adulthood are few.In this prospective case series, we aimed to assess safety and efficacy of burosumab in adolescents with XLH who discontinued long-term conventional therapy. MethodsFive Caucasian adolescents (4 males, 1 female; mean age 15.4 ± 1.5 years) with XLH were recruited and switched from conventional treatment to burosumab (0.8–1.2 mg/kg, s. c. QW2). Burosumab was continued for 12–48 months and, once discontinued, patients were followed-up for 6–12 months. In all patients, serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 1,25(OH)2D levels, and renal tubular reabsorption of phosphate (TmP/GFR) values were assessed at entry and during burosumab. Intact FGF23 plasma levels were measured at entry. Patient-reported outcomes (PROs) were assessed at entry and every 3–6 months to evaluate the impact of low extremity pain, stiffness, and difficulties performing daily activities. ResultsAt entry, all patients showed hypophosphatemia, increased intact FGF23 levels, reduced TmP/GFR, insufficient 1,25(OH)2D levels, and in four out of five increased ALP levels. Two patients had radiological signs of rickets. During burosumab, all patients showed a significant increase in serum phosphate and 1,25(OH)2D levels, and in TmP/GFR values (P < 0.05 - P < 0.0001). Serum ALP levels significantly declined (P < 0.05) to normal values. No changes of serum calcium and PTH levels (PNS) were found during burosumab. PROs significantly improved (P < 0.02 - P < 0.0001) in all patients. Four patients discontinued burosumab when they turned 18 or 19, whereas one continued the treatment since he was still younger than 18 during the study period. Four patients who suspended burosumab showed a rapid decline in serum phosphate and 1,25(OH)2D levels and in TmP/GFR values; serum ALP levels increased, and PROs progressively worsened with a significant reduction in quality of life. These consequences were not observed in the patient who continued burosumab treatment. DiscussionOur data showed that conventional treatment improved only in part the signs and symptoms of XLH. Burosumab was well tolerated and was effective in improving phosphate metabolism, bone health, and PROs. All the benefits of burosumab were lost after its discontinuation. These results suggested that continuing burosumab is required to achieve and maintain the clinical benefits of the treatment during the transition to young adulthood in patients with XLH.

A Comparative Analysis of Alkaline Phosphatase Levels in Gingival Crevicular Fluid of Patients Undergoing Growth Modulation Therapy With Twin Block, Forsus Fatigue Resistant, and Clear Block Appliances Compared to Normal Individuals: An In Vivo Study.

Background In the contemporary era, where science and technology know no boundaries, this in vivo study explores the impact of growth modulation therapy using Twin Block, Forsus Fatigue Resistant, and Clear Block appliances on alkaline phosphatase (ALP) levels in gingival crevicular fluid (GCF). Bone physiology involves modeling and remodeling, with orthodontics applying forces to teeth, influencing tissue reactivity and bone modeling. ALP, a marker of osteoblast function, plays a crucial role in bone growth. GCF reflects immunological and inflammatory responses during orthodontic force application, making it a valuable medium for studying ongoing metabolic processes related to bone turnover. Aim The study aims to comparatively analyze ALP levels in GCF during growth modulation therapy, assessing the efficacy of Twin Block, Forsus Fatigue Resistant, and Clear Block appliances. The research involves 30 experimental samples divided into three study groups and a control group. The samples are collected at various time intervals, and ALP levels are analyzed using a spectrophotometer. Statistical analysis includes paired and unpaired t-tests, one-way analysis of variance (ANOVA), and multiple comparisons. Results Results demonstrate a significant increase in ALP levels during the growth modulation therapy, indicating a positive correlation with bone remodeling. Twin Block appears to be the most effective appliance, exhibiting higher ALP activity compared to Clear Block and Forsus groups. Conclusion In conclusion, this study provides valuable insights into the biochemical responses during growth modulation therapy, emphasizing the potential of GCF analysis in understanding orthodontic treatment effects.

The Powdered Red Macroalgae (Eucheuma spinosum) Supplementation Potentially Enhanced Bone Structure in Osteoporotic Mice

BACKGROUND: Red macroalgae, such as Eucheuma spinosum, have been found to have potential benefits for bone health due to their unique bioactive compounds, including proteins, polyphenols, polysaccharides, vitamins, and minerals. Therefore, this study was conducted to evaluate the benefits of powdered E. spinosum supplementation in osteoporosis-induced mice.METHODS: Thirty middle-aged mice were divided into 6 groups, namely: healthy control group (HC), negative control group (NC), positive control group (PC), and treatment groups supplemented with 1.25 mg/gBW (T1), 2.5 mg/gBW (T2), and 5 mg/gBW (T3) of E. spinosum powder for twenty days. Mice in NC, PC, T1, T2, and T3 groups were induced with 0.0029 mg/gBW of dexamethasone for 30 days to create osteoporosis mice models. Alkaline phosphatase (ALP) levels were measured by colorimetric methods before and after the intervention. Bone structures were evaluated using X-ray images and histological examination.RESULTS: After the intervention, PC, T1, T2, and T3 groups showed a significant decrease (p≤0.01) in serum ALP levels compared to the NC group, which experienced an increase in ALP levels. The X-ray images revealed that the PC, T1, T2, and T3 showed radiopaque bone density. For bone histology, PC, T2, and T3 showed an improvement with thickened and intact trabeculae, but T1 still had visible osteoporosis cavities.CONCLUSION: Supplementation of 2.5 and 5 mg/gBW of E. spinosum powder were able to improve bone density as well bone histology. Therefore, E. spinosum powder supplementation might potentially improve bone structure in osteoporosis.KEYWORDS: Eucheuma spinosum, red macroalgae, alkaline phosphatase, osteoporosis

Changes in growth, morphology, and levels of digestive enzymes and growth-related hormones in early ontogeny of black scraper, Thamnaconus modestus

IntroductionThe black scraper, Thamnaconus modestus, is a highly valued marine fish species, but its output has gradually decreased in recent years, which may be due to its low survival rate during early ontogenesis.MethodsTherefore, in this study, we assessed the changes in growth, morphology, digestive enzymes, and hormone levels in T. modestus from 0–60 days post-hatching (dph) and revealed growth turning points by morphological measurement and determination of digestive enzyme activities and hormone levels. We found that ontogenesis could be divided into the larval (0–20 dph) and juvenile (20–60 dph) stages. Acid and alkaline protease activity significantly increased and decreased, respectively, from 12–25 dph, likely due to the development of stomach and gastric glands. Acid phosphatase levels significantly increased at 0 and 4 dph, which may be related to the regulation of metabolism and immune protection. A sharp increase in alkaline phosphatase levels at 20 and 25 dph was observed and was likely due to the development of the brush border membrane of enterocytes. The amylase level was significantly higher at 25, 30, and 35 dph, possibly due to better digestion and absorption during the transition from consuming Artemia to compound feed. In newly hatched larvae, the level of thyroid hormones triiodothyronine (T3) and thyroxine (T4) gradually increased and peaked at 35 dph, highlighting the importance of these hormones during the development of T. modestus. Growth hormone (GH) levels first increased from 0–8 dph, with a plateau at 8–20 dph, and then increased at 25–30–35 dph. For insulin-like growth factor 1 (IGF-1), a significant increase with a subsequent plateau was observed between 8 and 20 dph, followed by a substantial decrease between 30 and 35 dph. These results suggest that the regulating functions of GH and IGF-1 are synchronised. Digestive enzyme activity and hormone levels of abnormal fry at 30 dph were lower than those of normal fish, highlighting the importance of specific hormones, especially T4 and IGF-1, in the development of T. modestus.

Effect of ivermectin, amitraz and fipronil on midgut epithelium and digestive enzyme profile in Rhipicephalus microplus ticks (Acari: Ixodidae).

Blood feeding and digestion are vital physiological activities essential for the survival and reproduction of ticks. Chemical acaricides viz., ivermectin, amitraz and fipronil, are known to act on the central nervous system, resulting in the mortality of ticks. The present study is focused on the effect of these acaricides on the midgut and gut enzymes ofRhipicephalus microplus.The ultra-thin sections of midgut of ivermectin-treated ticks showed irregular basal membrane and ruptured digestive vesicles. Amitraz treatment resulted in a notable decrease in digestive cells with pleats in the basal membrane, while fipronil-exposed ticks exhibited reduced digestive cells, loss of cellular integrity, and disintegration of the basal membrane and muscle layer.The gut tissue homogenate of ivermectin and fipronil treated ticks showed a significant reduction of cathepsin D level, 76.54 ± 3.20 μg/mL and 92.67 ± 3.72 μg/mL, respectively, as compared to the control group (150.0 ± 3.80 μg/mL). The leucine aminopeptidase level (4.27 ± 0.08 units/mL) was significantly decreased in the ivermectin treated ticks compared to other treatment groups.The acid phosphatase activity (29.16 ± 0.67 μmole/min/L) was reduced in the ivermectin treated group whereas, increased activity was observed in the fipronil and amitraz treated groups. All the treatment groups revealed increased alkaline phosphatase levels (17.47-26.72 μmole/min/L). The present finding suggests that in addition to the established mechanism of action of the tested acaricides on the nervous system, the alterations in the cellular profile of digestive cells and enzymes possibly affect the blood digestion process and thus the synthesis of vital proteins which are essential for vitellogenesis, and egg production in ticks.

Dynamics of the functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy

The aim. To evaluate the dynamics of metabolic status, functional state of the liver and endothelium in patients with metabolic syndrome on the background of menopausal hormone therapy (MGT). Materials and methods. 40 menopausal women were examined, of which 25 patients with metabolic syndrome with an average age of 51.2 ± 1.2 years and 15 practically healthy women of 50.2 ± 1.9 years. anamnesis was collected, the presence of vasomotor symptoms was assessed, anthropometric data was measured with the calculation of body mass index, laboratory examination, including determination of blood levels of sex hormones, functional liver tests, metabolic parameters and markers of endothelial dysfunction- endothelin-1, vascular endothelial growth factor, the number of desquamated endotheliocytes and the activity of Willebrand factor, instrumental examination, including ultrasound examination of the liver and assessment of the vascular response to local heating on the Microtest device (Russia), as well as calculation of the Hepatic steatosis index (HSI). Results. In patients with metabolic syndrome in menopause, vasomotor symptoms, complaints of dysuria, dyspeptic phenomena were observed, an increase in blood pressure was recorded in 60%, an increase in Kurlov’s ordinates in 24%, 36% were overweight, 64% were obese 1-2 degrees. According to ultrasound, liver steatosis was verified in 76% of patients, the HSI index &gt;36.0 was in all women with MS. Against the background of estrogen deficiency, the course of menopause in women was accompanied by insulin resistance, dyslipidemia, increased alkaline phosphatase levels in 28% of individuals and endothelial dysfunction with impaired physiological response to local heating, increased vascular tone, increased thrombogenic potential of the vascular wall and activation of angiogenesis mechanisms. Conclusion: MGT with Femoston ® 1 in continuous mode in women with metabolic syndrome reduces the severity of menopausal syndrome, insulin resistance and liver steatosis, improves anthropometric parameters and functional characteristics of the liver and endothelium, which reduces the risk of cardiovascular events in this risk group.

Spectrum of Liver Injury in Dengue Fever: Cause or Effect of Severe Dengue?

The study aimed to determine if deranged liver function tests (LFTs) can predict severe dengue or mortality. It included 135 dengue patients, with a mean age of 30.9 ± 12.09 years. Among the patients, 82 (60.7%) were under 30 years of age. Nearly half of the patients (64, 47. 4%) had some degree of liver damage indicated by deranged LFTs, 27 (42.1%) had elevated alanine transaminase (ALT), 7 (10.9%) had increased bilirubin, and 30 (46.9%) had high values of alkaline phosphatase (ALP). However, only elevated ALP levels were positively correlated with mortality (Pearson's R = 0.282, p = <0.05). The mean bilirubin was 11.711 ± 8.602 umol/l, and the mean values of ALT and ALP were 107 ± 240 and 113.571 ± 59.91 IU/L, respectively, which were higher than the normal. The study findings suggested that hepatic derangement is a common occurrence in dengue patients, and increased ALP levels could be an indicator of a higher risk of mortality. These findings can help improve patient care by identifying the potential risk factors for mortality. Key Words: Dengue, Liver function tests, Alanine transaminase, Alkaline phosphatase.

Evaluation of autoimmune liver disease natural history in patients referred to Middle East Liver Diseases (MELD) center

BackgroundAutoimmune liver diseases (AILD) are increasing and common forms of chronic liver disease (CLD) with different clinical responses and characteristics which can result in cirrhosis. This study aimed to investigate the natural history and characteristics of AILD in an Iranian population.MethodsPatients with AILD [Autoimmune Hepatitis (AIH), Primary Biliary Cholangitis (PBC), Primary Sclerosing Cholangitis (PSC) and Overlap Syndrome (OS)] referred to Middle East Liver Diseases (MELD) center, Tehran, Iran, between January 2002 and December 2022 were included in this retrospective cohort study. The main features of natural history (the trends of liver functional tests (LFT), Auto-Antibodies, response to treatment and cirrhotic status) along with demographic data were studied.ResultsTwo hundred sixty-five patients (160 (60.4%) AIH, 37 (14.0%) PBC, 20 (7.5%) PSC, 48 (18.1%) overlap syndrome) with a median follow-up time of 5 years (IQR 4 to 8 years) were included. Baseline laboratory tests revealed that patients with AIH exhibit elevated transaminase levels. However, patients suffering from PBC and PSC displayed increased alkaline phosphatase levels. Conversely, in overlap syndrome patients, both transaminases and alkaline phosphatase were observed at high levels. Autoantibodies represented themselves as important diagnostic markers for the AIH and PBC but not for PSC. The complete response occurred in 112 (70%) of and 28 (58.4%) patients with AIH and overlap syndrome respectively and 21 patients 11 (6.9%) of AIH and 10 (20.8%) of overlap syndrome) were non-responders. Other patients in these two categories were considered as insufficient responders. On the other side, 32 (91.9%) and 8 (40%) of patients with PBC and PSC biochemically responded to Ursodeoxycholic Acid (UDCA). Unpredictably, cirrhosis regression was observed in some AIH and PBC patients.ConclusionAppropriate medication management for AILD patients may leads to regression from cirrhosis and improvement of manifestations; while discontinuation of medication may cause relapses. However, patient suffering from PSC showed limited response to treatment.

Associated factors with liver fibrosis in rheumatoid arthritis patients treated with methotrexate.

There are conflicting findings on the link between liver fibrosis and cumulative methotrexate dosages. We aimed to determine the frequency of liver fibrosis in rheumatoid arthritis patients treated with methotrexate and to identify its associated factors. We conducted a cross-sectional study over 9 months (April-December 2021), including rheumatoid arthritis patients treated with methotrexate. Demographic and clinical data were collected. Liver stiffness was assessed by FibroScan. Fibrosis and significant liver fibrosis were defined as liver stiffness higher than 6 and 7.2 kPa, respectively. Liver tests, albuminemia, lipid profile, and blood glycemia were measured. Metabolic syndrome was also evaluated. Statistical analyses were performed using SPSS. We included 21 men and 47 women. The mean age was 51.60 ± 1.82 years. The mean disease duration was 8.29 ± 6.48 years. The mean weekly intake of methotrexate was 13.76 ± 3.91 mg. The mean methotrexate duration was 4.67 ± 4.24 years. The mean cumulative dose was 3508.87 ± 3390.48 mg. Hypoalbuminemia and metabolic syndrome were found in 34% and 25% of cases. We noted increased alkaline phosphatase levels in four cases. The mean liver stiffness was 4.50 ± 1.53kPa. Nine patients had liver fibrosis, and four had significant fibrosis. Associated factors with liver fibrosis were as follows: age ≥ 60 years (OR:22.703; 95%CI [1.238-416.487]; p = 0.035), cumulated dose of methotrexate ≥ 3 g (OR: 76.501; 95%CI [2.383-2456.070]; p = 0.014), metabolic syndrome (OR: 42.743; 95%CI [1.728-1057.273]; p = 0.022), elevated alkaline phosphatase levels (OR: 28.252; 95%CI [1.306-611.007]; p = 0.033), and hypoalbuminemia (OR: 59.302; 95%CI [2.361-1489.718]; p = 0.013). Cumulating more than 3 g of methotrexate was associated with liver fibrosis in rheumatoid arthritis patients. Having a metabolic syndrome, higher age, hypoalbuminemia, and elevated alkaline phosphatase levels were also likely to be independently associated with liver fibrosis. Key points • Rheumatoid arthritis patients require monitoring hepatic fibrosis when the cumulated dose of methotrexate is above 3 g. • Metabolic syndrome is a risk factor for liver fibrosis, suggesting that its management is necessary to prevent this complication. • Hypoalbuminemia and elevated alkaline phosphatase levels (twice the upper limit) in rheumatoid arthritis patients treated with methotrexate were associated with liver fibrosis.

Rare Case of Candida Parapsilosis Empyema Thoracis

BACKGROUND: This case report describes a patient with pleural empyema that grew Candida parapsilosis, an unexpected finding, especially in an immunocompetent individual with no prior surgery or trauma to the area. Candida empyema is a rare infection associated with mortality rates as high as 61.9%. METHODS: A 63-year-old male with a past medical history of pulmonary emboli was in his usual state of health when he developed worsening left-sided chest pain over 3 days, with associated shortness of breath and productive cough that was blood-tinged on occasion. Extensive imaging and a diagnostic thoracentesis confirmed an expanding left-sided parapneumonic effusion that was drained and found to grow Streptococcus anginosis and Candida parapsilosis. During his hospitalization, the patient also demonstrated increased alkaline phosphatase levels without abdominal pain or elevation in AST, ALT, or bilirubin, prompting further diagnostic imaging. Ultrasound of the abdomen showed a large, heterogeneous liver; follow-up CT scan, which was done without contrast due to worsening acute kidney injury, did not rule out liver masses. The patient’s clinical condition began to significantly improve following drainage of the pleural effusion and removal of the chest tube. After his kidney function returned to baseline, the patient was discharged with the remainder of his 18-day courses of amoxicillin-clavulanate and fluconazole, with a contrasted CT of the abdomen scheduled in the outpatient setting. CONCLUSION: This is an unusual case of fungal empyema, a severe manifestation of invasive candidiasis with a poor prognosis. Given the paucity of studies on Candida empyema, there is no definitive treatment for this deadly infection. A 2021 retrospective study of 81 patients with Candida empyema at two academic centers posited that optimal management included pleural drainage and fluconazole treatment. The same study found that 20% of Candida empyema originated from intra-abdominal sources. As for the patient in this case report, there remains the possibility that upcoming outpatient contrasted CT imaging of the abdomen will reveal the source of his infection.

Relationships among body weight, lipids and bone mass in elderly individuals with fractures: A case-control study.

The prevalence of osteoporosis and low bone mass is steadily rising each year. Low body weight is commonly linked to diminished bone mass and serves as a robust predictor of osteoporosis. Nonetheless, the connection between body mass index (BMI), bone mineral density, and lipid profiles among the elderly remains elusive. To examine the association between BMI and bone mass, explore the correlation between lipid profiles and bone mass, and delve into the interplay between lipid metabolism and bone health. The study included 520 patients aged ≥ 65 years (178 men and 342 women). Age, sex, weight, and height were recorded. Femoral neck bone mineral density and T scores were determined using a dual-energy X-ray absorptiometry scanner. Blood calcium (Ca), phosphorus (P), albumin (ALB), alkaline phosphatase (ALP), aspartate aminotransferase, alanine aminotransferase, triglyceride (TG), total cholesterol (TC), high-density lipoprotein (HDL) and low-density lipoprotein (LDL) levels were measured. Patients were classified by sex (male and female), age (65-79 years and ≥ 80 years), and T score (normal bone mineral density, osteopenia and osteoporosis). Age, sex, BMI, and ALP and TG levels were independent risk factors for osteoporosis. For the 65-79- and ≥ 80-year-old groups, females presented lower T scores than males. Ca, P, ALB, ALP, TC, HDL and LDL levels were significantly different between men and women in the 65-79-year-old group. In addition, BMI and TG levels were significantly decreased in osteoporotic patients compared with patients with normal bone mass. TC levels declined in 65- to 79-year-old male and female osteoporosis patients. In the group of women aged ≥ 80 years, osteoporotic patients showed significantly increased ALP levels. Furthermore, we found positive correlations between BMI and TG levels in the male and female patient groups. However, we found no significant differences in ALB, Ca, P, HDL and LDL levels in osteoporotic patients compared to patients with normal bone mass. Osteoporotic patients showed significantly decreased BMI and TG levels compared with those with normal bone mass. BMI showed positive correlations with TG levels in male and female patients. These results indicate correlations between BMI and bone mass and between lipid profiles and bone mass.

Unveiling the Osteogenic Potential of Tetracyclines: A Comparative Study in Human Mesenchymal Stem Cells.

Tetracyclines (TCs) are a class of broad-spectrum antibiotics with diverse pharmacotherapeutic properties due to their various functional groups being attached to a common core structure. Beyond their antibacterial activity, TCs trigger pleiotropic effects on eukaryotic cells, including anti-inflammatory and potentially osteogenic capabilities. Consequently, TCs hold promise for repurposing in various clinical applications, including bone-related conditions. This study presents the first comprehensive comparison of the in vitro osteogenic potential of four TCs-tetracycline, doxycycline, minocycline, and sarecycline, within human mesenchymal stem cells. Cultures were characterized for metabolic activity, cell morphology and cytoskeleton organization, osteogenic gene expression, alkaline phosphatase (ALP) activity, and the activation of relevant signaling pathways. TCs stimulated actin remodeling processes, inducing morphological shifts consistent with osteogenic differentiation. Osteogenic gene expression and ALP activity supported the osteoinduction by TCs, demonstrating significant increases in ALP levels and the upregulation of RUNX2, SP7, and SPARC genes. Minocycline and sarecycline exhibited the most potent osteogenic induction, comparable to conventional osteogenic inducers. Signaling pathway analysis revealed that tetracycline and doxycycline activate the Wnt pathway, while minocycline and sarecycline upregulated Hedgehog signaling. Overall, the present findings suggest that TCs promote osteogenic differentiation through distinct pathways, making them promising candidates for targeted therapy in specific bone-related disorders.

In Vitro Study of Composite Cements on Mesenchymal Stem Cells of Palatal Origin

Uniform filler distribution in composites is an important requirement. Therefore, BaO glass, nano hydroxyapatite and quartz filler distribution was realized through PCL microcapsules which progressively release filler during matrix polymerization. Two composites were realized based on a complex matrix containing BisGMA, UDMA, HEMA and PEG400 mixed with a previously described mineral filler: 33% for C1 and 31% for C2. The spreading efficiency was observed via SEM, revealing a complete disintegration of the microcapsules during C1 polymerization, while C2 preserved some microcapsule parts that were well embedded into the matrix beside BaO filler particles; this was confirmed by means of the EDS spectra. Mesenchymal stem cells of palatal origin were cultured on the composites for 1, 3, 5 and 7 days. The alkaline phosphatase (ALP) level was measured at each time interval and the cytotoxicity was tested after 3, 5 and 7 days of co-culture on the composite samples. The SEM investigation showed that both composites allowed for robust proliferation of the cells. The MSC cell pluripotency stage was observed from 1 to 3 days with an average level of ALP of 209.2 u/L for C1 and 193.0 u/L for C2 as well as a spindle cell morphology. Cell differentiation occurred after 5 and 7 days of culture, implied by morphological changes such as flattened, star and rounded shapes, observed via SEM, which were correlated with an increased ALP level (279.4 u/L for C1 and 284.3 u/L for C2). The EDX spectra after 7 days of co-culture revealed increasing amounts of P and Ca close to the hydroxyapatite stoichiometry, indicating the stimulation of the osteoinductive behavior of MSCs by C1 and C2. The MTT assay test showed a cell viability of 98.08% for C1 and 97.33% for C2 after 3 days, proving the increased biocompatibility of the composite samples. The cell viability slightly decreased at 5 and 7 days but the results were still excellent: 89.5% for C1 and 87.3% for C2. Thus, both C1 and C2 are suitable for further in vivo testing.

Ursodeoxycholic Acid Use After Bariatric Surgery: Effects on Metabolic and Inflammatory Blood Markers

BackgroundIn addition to the reduction of symptomatic gallstone disease, ursodeoxycholic acid (UDCA) might also have beneficial metabolic effects after bariatric surgery. We examined the impact of UDCA on liver enzymes, hemoglobin A1c (HbA1c), lipids, and inflammation markers.MethodsPatients in the UPGRADE trial (placebo-controlled, double-blind) were randomized between UDCA 900 mg daily or placebo pills for 6 months after bariatric surgery. Patients without blood measurements pre- or 6 months postoperatively were excluded. The change in liver enzymes, Hba1c, lipids, and inflammation markers after surgery were compared between the UDCA and placebo group, followed by a postoperative cross-sectional comparison.ResultsIn total, 513 patients were included (age [mean ± SD] 45.6 ± 10.7 years; 79% female). Preoperative blood values did not differ between UDCA (n = 266) and placebo (n = 247) groups. Increase of alkaline phosphatase (ALP) was greater in the UDCA group (mean difference 3.81 U/l [95%CI 0.50 7.12]). Change in other liver enzymes, HbA1c, lipids, and CRP levels did not differ. Postoperative cross-sectional comparison in 316 adherent patients also revealed a higher total cholesterol (mean difference 0.25 mg/dl [95%CI 0.07–0.42]), lower aspartate aminotransferase (mean difference −3.12 U/l [−5.16 – −1.08]), and lower alanine aminotransferase level (mean difference −5.89 U/l [−9.41 – −2.37]) in the UDCA group.ConclusionUDCA treatment leads to a higher, but clinically irrelevant increase in ALP level in patients 6 months after bariatric surgery. No other changes in metabolic or inflammatory markers were observed. Except for the reduction of gallstone formation, UDCA has no effects after bariatric surgery.Graphical

Effect of Simvastatin Administration on ALP (Alkaline Phosphatase) Level in Wistar Rat's Femur Fracture

Metabolism of the bone healing process can be monitored by Bone formation marker, such as alkaline phosphate (ALP). Simvastatin is known to increase bone marker formation in the repair phase, but its effects on the ALP level have not been known yet. This study aimed to determine the effect of oral simvastatin administration on the expression of ALP level in femur fracture healing in a rat model of femur fracture. The research method was experimental post-test only using 18 Rattus norvegicus rats which were divided into 3 groups, namely the control group for femur fracture (Control), femoral fracture group and giving simvastatin 0.36 mg/day for 2 weeks (Treatment I), and femur fracture group and administration of simvastatin 0.36 mg/day for 4 weeks (Treatment II). ALP levels were measured at 0, 2, and 4 weeks. The results showed an increase in ALP levels in the simvastatin treatment group compared to the control group (p&lt;0.05). It can be concluded that the administration of simvastatin increased ALP levels in rat femoral fractures.

Elevated serum alkaline phosphatase correlates with postoperative cognitive dysfunction: A retrospective cohort study based on STROBE statement.

Little is known about the association between serum alkaline phosphatase (ALP) levels and postoperative cognitive dysfunction (POCD) after general anesthesia. Thus, we investigated the association of serum ALP levels with POCD in patients who underwent surgery with general anesthesia in a retrospective cohort study. We retrospectively collected data from patients who underwent surgery with general anesthesia between May 2016 and June 2020. Serum ALP activity was detected using a p-nitrophenyl phosphate assay. Pre-and postoperative cognitive function were evaluated using the Chinese version of the Mini-Mental State Examination. Univariate and multivariate logistic regression were used to explore the effect of ALP on cognitive function. The incidence of POCD was 13.5%. Compared with the control group, the POCD group had higher ALP levels. The neuropsychological test results suggested that the scores of most items were lower in the POCD group than in the non-POCD group. Univariate logistic regression indicated that increased ALP levels were significantly associated with cognitive dysfunction (odds ratio = 1.15, 95% confidence interval: 1.13-1.18, P = .000). Multivariate regression showed that elevated ALP was still associated with POCD after adjusting for confounding factors (odds ratio = 1.16, 95% confidence interval: 1.13-1.18, P = .000). The spline regression model indicated the dose-response associations between ALP level and POCD risk (P for nonlinear trend < .001). Our study indicated that elevated serum ALP was an independent predictive factor of POCD at the 3-month follow-up. The occurrence of POCD could be associated with inflammatory status.

Changes in Serum Alkaline Phosphatase, Calcium, and Parathyroid Hormone with Different Doses of Iodine Therapy:.

Background: Despite the benefits of radioactive iodine (RAI) therapy as an adjunctive treatment for thyroid cancer, it can be associated with several side effects. The main purpose of this study was to determine the changes in serum alkaline phosphatase (ALP), calcium (Ca), and parathyroid hormone (PTH) at different doses of RAI therapy among patients who were referred to the nuclear medicine department of Namazi Hospital, Shiraz. Materials and Methods: This cross-sectional study was conducted on 60 patients with papillary thyroid cancer who underwent RAI therapy at different doses of 100, 150, and 200 mCi. The ALP, Ca, and PTH levels of patients were measured before and 60 days after RAI therapy. Results: Our study revealed that RAI therapy at all doses significantly increased ALP level in comparison with baseline amounts (P≤0.05). However, changes in PTH and Ca levels were not significant among patients who received different doses of RAI (P˃0.05). Conclusion: RAI therapy could affect important hormones and enzymes such as ALP and PTH. This issue can be considered in diagnostic and therapeutic prescriptions of RAI for the treatment of thyroid cancer.[GMJ.2022;11:e2397].

Association between serum alkaline phosphatase and bacteraemia in haemodialysis outpatients: a multicentre retrospective cross-sectional study

ObjectivesElevated baseline serum alkaline phosphatase (ALP) may correlate with higher medium-term to long-term mortality in the general population and in patients with chronic kidney disease. However, few data are available...