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What is the ultimate goal in acid-base regulation?

Balakrishnan S, Gopalakrishnan M, Alagesan M, Prakash ES

Adv Physiol Educ, 2007 Mar;31(1):51-4.
PMID: 17327583

It is common to see chapters on acid-base physiology state that the goal of acid-base regulatory mechanisms is to maintain the pH of arterial plasma and not arterial Pco(2) (Pa(CO(2))) or plasma HCO(3). A hypothetical situation in which the Pa(CO(2)) of arterial plasma is 80 mmHg and the plasma HCO(3) concentration is 48 mM is presented and analyzed to get over this misconception. As per the modified Henderson equation, the pH of arterial plasma would be 7.4; however, we explain that this may be associated with intracellular acidosis due to intracellular hypercapnia and that derangement of homeostasis is evident from the occurrence of respiratory depression and, eventually, coma in the patient described. This suggests that the ultimate goal of acid-base regulatory mechanisms is not just the maintenance of the pH of arterial plasma but the maintenance of the steady-state pH of intracellular fluid as well.

Matched MeSH terms: Homeostasis/physiology
Brain biometals and Alzheimer's disease - boon or bane?

Prakash A, Dhaliwal GK, Kumar P, Majeed AB

Int J Neurosci, 2017 Feb;127(2):99-108.
PMID: 27044501

Alzheimer's disease (AD) is the most common form of dementia. Several hypotheses have been put forward to explain the basis of disease onset and progression. A complicated array of molecular events has been implicated in the pathogenesis of AD. It is attributed to a variety of pathological conditions that share similar critical processes, such as oxidative stress, proteinaceous aggregations, mitochondrial dysfunctions and energy failure. There is increasing evidence suggesting that metal homeostasis is dysregulated in the pathology of AD. Biometals play an important role in the normal body functioning but AD may be mediated or triggered by disproportion of metal ions leading to changes in critical biological systems and initiating a cascade of events finally leading to neurodegeneration and cell death. The link is multifactorial, and although the source of the shift in oxidative homeostasis is still unclear, current evidence points to changes in the balance of redox transition metals, especially iron, copper (Cu) and other trace metals. Their levels in the brain are found to be elevated in AD. In other neurodegenerative disorders, Cu, zinc, aluminum and manganese are involved. This paper is a review of recent advances of the role of metals in the pathogenesis and pathophysiology of AD and related neurodegenerative diseases.

Matched MeSH terms: Homeostasis/physiology
Fulltext The relationship between telomere length and beekeeping among Malaysians

Nasir NF, Kannan TP, Sulaiman SA, Shamsuddin S, Azlina A, Stangaciu S

Age (Dordr), 2015 Jun;37(3):9797.
PMID: 26028466 DOI: 10.1007/s11357-015-9797-6

The belief that beekeepers live longer than anyone else is present since ages. However, no research has been done to explore the longevity of life in beekeepers. Here, we investigated the telomere length in 30 male beekeepers and 30 male non-beekeepers and associated them with the longevity of life using Southern analysis of terminal restriction fragments (TRFs) generated by Hinf I/Rsa I digestion of human genomic DNA using TeloTAGGG Telomere Length Assay. Interestingly, we found that the telomere length of male beekeepers was significantly longer than those of male non-beekeepers with a p value of less than 0.05, suggesting that beekeepers may have longer life compared to non-beekeepers. We further found that the consumption of bee products for a long period and frequent consumption of bee products per day are associated with telomere length. An increase of year in consuming bee products is associated with a mean increase in telomere length of 0.258 kbp. In addition, an increase in frequency of eating bee products per day was also associated with a mean increase of 2.66 kbp in telomere length. These results suggested that bee products might play some roles in telomere length maintenance.

Matched MeSH terms: Telomere Homeostasis/physiology*
Autophagy and senescence: A new insight in selected human diseases

Rajendran P, Alzahrani AM, Hanieh HN, Kumar SA, Ben Ammar R, Rengarajan T, et al.

J Cell Physiol, 2019 12;234(12):21485-21492.
PMID: 31144309 DOI: 10.1002/jcp.28895

Senescence and autophagy play important roles in homeostasis. Cellular senescence and autophagy commonly cause several degenerative processes, including oxidative stress, DNA damage, telomere shortening, and oncogenic stress; hence, both events are known to be interrelated. Autophagy is well known for its disruptive effect on human diseases, and it is currently proposed to have a direct effect on triggering senescence and quiescence. However, it is yet to be proven whether autophagy has a positive or negative impact on senescence. It is known that elevated levels of autophagy induce cell death, whereas inadequate autophagy can trigger cellular senescence. Both have important roles in human diseases such as aging, renal degeneration, neurodegenerative disorders, and cancer. Therefore, this review aims to highlight the relevance of senescence and autophagy in selected human ailments through a summary of recent findings on the connection and effects of autophagy and senescence in these diseases.

Matched MeSH terms: Homeostasis/physiology
Homeostatic indices of insulin resistance among gestational diabetics in anticipating pregnancy complications

Ismail NA, Kasim MM, Noor Aizuddin A, Umar NA

Gynecol Endocrinol, 2013 Jul;29(7):691-4.
PMID: 23772780 DOI: 10.3109/09513590.2013.797398

OBJECTIVE: This was to determine HOMA-IR score as well as to assess its association in fetal and maternal outcomes among pregnant women with diabetes risks.
METHODS: A prospective cohort study of pregnant women with diabetes risks was done. GDM was diagnosed using modified glucose tolerance test. Serum insulin was taken and measured by an electrochemiluminescence immunoassay method. Plasma glucose was measured by enzymatic reference method with hexokinase. HOMA-IR score was calculated for each patient. Maternal and fetal outcomes were analyzed.
RESULTS: From 279 women recruited, 22.6% had GDM with higher HOMA-IR score (4.07 ± 2.44 versus 2.08 ± 1.12; p = 0.001) and fasting insulin (16.76 ± 8.63 µIU/L versus 10.15 ± 5.07 µIU/L; p = 0.001). Area under ROC curve for HOMA-IR score was 0.79 (95% confidence interval, 0.74-0.84) with optimum cut-off value of 2.92 (sensitivity = 63.5%; specificity = 89.8%), higher than recommended by IDF (2.38). This point showed significant association with neonatal hypoglycemia (p = 0.02) and Cesarean section (p = 0.04) in GDM mothers.
CONCLUSIONS: HOMA-IR score and insulin resistance levels were higher in GDM women in our population. With the cut-off HOMA-IR value of 2.92, neonatal hypoglycemia and Cesarean section were significant complications in GDM mothers. This can be used in anticipation of maternal and fetal morbidities.

Matched MeSH terms: Homeostasis/physiology*
Zinc: indications in brain disorders

Prakash A, Bharti K, Majeed AB

Fundam Clin Pharmacol, 2015 Apr;29(2):131-49.
PMID: 25659970 DOI: 10.1111/fcp.12110

Zinc is the authoritative metal which is present in our body, and reactive zinc metal is crucial for neuronal signaling and is largely distributed within presynaptic vesicles. Zinc also plays an important role in synaptic function. At cellular level, zinc is a modulator of synaptic activity and neuronal plasticity in both development and adulthood. Different importers and transporters are involved in zinc homeostasis. ZnT-3 is a main transporter involved in zinc homeostasis in the brain. It has been found that alterations in brain zinc status have been implicated in a wide range of neurological disorders including impaired brain development and many neurodegenerative disorders such as Alzheimer's disease, and mood disorders including depression, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, and prion disease. Furthermore, zinc has also been implicated in neuronal damage associated with traumatic brain injury, stroke, and seizure. Understanding the mechanisms that control brain zinc homeostasis is thus critical to the development of preventive and treatment strategies for these and other neurological disorders.

Matched MeSH terms: Homeostasis/physiology
Fulltext Symptomatic presentation of carotid sinus hypersensitivity is associated with impaired cerebral autoregulation

Tan MP, Chadwick TJ, Kerr SR, Parry SW

J Am Heart Assoc, 2014 Jun;3(3):e000514.
PMID: 24947997 DOI: 10.1161/JAHA.113.000514

Carotid sinus hypersensitivity (CSH) is associated with syncope, unexplained falls, and drop attacks in older people but occurs asymptomatically in 35% of community-dwelling elders. We hypothesized that impaired cerebral autoregulation is associated with the conversion of asymptomatic CSH to symptomatic CSH. We therefore conducted a case-control study evaluating individuals with CSH with and without the symptoms of syncope or unexplained falls, as well as non-CSH controls, to determine whether the blood pressure and heart rate changes associated with CSH are associated with symptoms only when cerebral autoregulation is altered.

Matched MeSH terms: Homeostasis/physiology
New insights into seaweed polyphenols on glucose homeostasis

Murugan AC, Karim MR, Yusoff MB, Tan SH, Asras MF, Rashid SS

Pharm Biol, 2015 Aug;53(8):1087-97.
PMID: 25630358 DOI: 10.3109/13880209.2014.959615

CONTEXT: Polyphenol-rich marine macroalgae are gaining dietary importance due to their influence over diabetes mellitus and the role as a vital source of high-value nutraceuticals. Their assorted beneficial effects on human health include competitive inhibition of digestive enzymes, varying the activity of hepatic glucose-metabolizing enzymes, lowering the plasma glucose levels, and lipid peroxidation, delaying the aging process.
OBJECTIVE: In this paper, we review the health beneficial effects of polyphenols and phlorotannins from brown seaweeds with special emphasis on their inhibitory effects on carbohydrate-metabolizing enzymes.
METHODS: A survey of literature from databases such as Sciencedirect, Scopus, Pubmed, Springerlink, and Google Scholar from the year 1973 to 2013 was done to bring together the information relating to drug discovery from brown seaweeds as a source for diabetes treatment.
RESULTS: Over the past two decades, 20 different bioactive polyphenols/phlorotannins have been isolated and studied from 10 different brown algae. Discussion of the positive effect on the inhibition of enzymes metabolizing carbohydrates in both in vitro and in vivo experiments are included.
CONCLUSION: Despite the recent advancements in isolating bioactive compounds from seaweeds with potential health benefit or pharmaceutical behavior, studies on the polyphenol effectiveness on glucose homeostasis in human beings are very few in response to their functional characterization. Added research in this area is required to confirm the close connection of polyphenol rich seaweed-based diet consumption with glucose homeostasis and the exciting possibility of prescribing polyphenols to treat the diabetes pandemic.

Matched MeSH terms: Homeostasis/physiology
Fulltext Systemic VEGF-A neutralization ameliorates diet-induced metabolic dysfunction

Wu LE, Meoli CC, Mangiafico SP, Fazakerley DJ, Cogger VC, Mohamad M, et al.

Diabetes, 2014 Aug;63(8):2656-67.
PMID: 24696450 DOI: 10.2337/db13-1665

The vascular endothelial growth factor (VEGF) family of cytokines are important regulators of angiogenesis that have emerged as important targets for the treatment of obesity. While serum VEGF levels rise during obesity, recent studies using genetic models provide conflicting evidence as to whether VEGF prevents or accelerates metabolic dysfunction during obesity. In the current study, we sought to identify the effects of VEGF-A neutralization on parameters of glucose metabolism and insulin action in a dietary mouse model of obesity. Within only 72 h of administration of the VEGF-A-neutralizing monoclonal antibody B.20-4.1, we observed almost complete reversal of high-fat diet-induced insulin resistance principally due to improved insulin sensitivity in the liver and in adipose tissue. These effects were independent of changes in whole-body adiposity or insulin signaling. These findings show an important and unexpected role for VEGF in liver insulin resistance, opening up a potentially novel therapeutic avenue for obesity-related metabolic disease.

Matched MeSH terms: Homeostasis/physiology
Effects of glycyrrhizic acid on 11 β-hydroxysteroid dehydrogenase (11 βHSD1 and 2) activities and HOMA-IR in rats at different treatment periods

Chia YY, Yin YY, Ton SH, Kadir KB

Exp. Clin. Endocrinol. Diabetes, 2010 Oct;118(9):617-24.
PMID: 19998240 DOI: 10.1055/s-0029-1237703

Glycyrrhizic acid (GA) has been reported to inhibit postprandial blood glucose rise and 11 β-hydroxysteroid dehydrogenase 1 (11 βHSD1) activity. As not much work has been done on GA effects on 11 βHSD1 and 2 and HOMA-IR at different treatment periods, this work was conducted. 60 male Sprague Dawley rats fed AD LIBITUM were assigned into six groups of control and treated that were given GA at different duration namely 12, 24 and 48 h. Treated and control groups were intraperitoneally administered with GA (50 mgkg (-1)) and saline respectively. Blood and subcutaneous (ATS) and visceral adipose tissue (ATV), abdominal (MA) and quadriceps femoris muscle (MT), liver (L) and kidney (K) were examined. HOMA-IR in GA-treated rats decreased in all groups (P<0.05). In the 12-h and 24-h treated rats, 11 βHSD1 activities decreased in all tissues (P<0.05) except MA and MT (P>0.05) in the former and ATV (P>0.05) in the latter. However, 11 βHSD1 activities decreased significantly in all tissues ( P<0.05) in the 48-h treated rats. Significant decrease in 11 βHSD2 (P>0.05) activities were observed in the L of all treatment groups and K in the 24-h and 48-h treated rats (P<0.05). Histological analysis on ATS showed increase in the number of small-size adipocytes while ATV adipocytes showed shrinkage after GA administration. Increased glycogen deposition in the L was observed in the GA-administered rats in all the treatment periods. In conclusion, GA treatment showed a decrease in the HOMA-IR and both 11 βHSD1 and 2 activities in all tissues, with more profound decrease in the 48-h treated rats.

Matched MeSH terms: Homeostasis/physiology