Normal Blood pH Research Articles

Ischemic stroke: focus on hyperuricemia

Uric acid is a weak organic acid with a molecular weight of 168.112 g/mol. Most uric acid at normal blood pH circulates as urates, negatively charged weak salts derived from uric acid. Being the end product of the process of purine catabolism, uric acid is excreted from the human body in urine until kidney function is impaired. Hyperuricemia may occur due to decreased excretion, increased production, or a combination of both mechanisms. Over the past decades, several studies in the adult population have attempted to establish the correlation between the risk of stroke and serum uric acid concentrations, and how these levels influence the patient's neurological outcome after stroke. Our review is devoted to the study of the mechanisms of normal purine metabolism, disorders of purine metabolism and pathogenetic mechanisms of the development of ischemic stroke in hyperuricemia.

Nanoformulation of Paclitaxel: Exploring the Cyclodextrin / PLGA Nano Delivery Carrier to Slow Down Paclitaxel Release, Enhance Accumulation in Vivo.

Background: Improving the aggregation and penetration in tumor sites increases the anti-tumor efficacy of nanomedicine. In the current study, we designed cyclodextrin modified PLGA nanoparticles loaded with paclitaxel to elevate the accumulation and prolong circulation of chemotherapy drugs in vivo. Methods: The PLGA nanoparticles loaded with paclitaxel (PTX PLGA NPs) and cyclodextrin (CD) modified PLGA nanoparticles loaded with paclitaxel (PTX PLGA/CD NPs) were prepared using the emulsification solvent evaporation method. The nanoparticles were characterized by particle size, zeta potential, encapsulation efficiency, infrared spectroscopy analysis and X-Ray diffraction (XRD). Then, drug release of the nanoparticles was evaluated via reverse dialysis method in vitro. Finally, the in vivo distribution fate and pharmacokinetic characteristics of the nanoparticles were assessed in mice and rats. Results: The average particle size, zeta potential, and encapsulation efficiency of PTX PLGA NPs were (163.57±2.07) nm, - (20.53±2.79) mV and (60.44±6.80)%. The average particle size, zeta potential, and encapsulation efficiency of PTX PLGA/CD NPs were (148.57±1.66) nm, - (11.42±0.84) mV and (85.70±2.06)%. In vitro release studies showed that PTX PLGA/CD NPs were released more slowly compared to PTX PLGA NPs under normal blood pH conditions, while PTX PLGA/CD NPs were released more completely under tumor site pH conditions. The modified PLGA nanocarrier (PLGA/CD NPs) increased drug residence time and accumulation than the plain PLGA nanocarrier (PLGA NPs) in vivo distribution. In addition, the elimination half-life, area under the drug-time curve, and maximum blood concentration of the nanoparticle group were higher than those of Taxol®, especially the PTX PLGA/CD NPs group, which was significantly different from Taxol® and plain nanoparticle groups (p<0.001). Conclusions: The 2-HP-β-CD modified PLGA nanoparticles prolonged circulation time and accumulation of the chemotherapy drug paclitaxel in vivo.

Gut Microbiota Functional Traits, Blood pH, and Anti-GAD Antibodies Concur in the Clinical Characterization of T1D at Onset.

Alterations of gut microbiota have been identified before clinical manifestation of type 1 diabetes (T1D). To identify the associations amongst gut microbiome profile, metabolism and disease markers, the 16S rRNA-based microbiota profiling and 1H-NMR metabolomic analysis were performed on stool samples of 52 T1D patients at onset, 17 T1D siblings and 57 healthy subjects (CTRL). Univariate, multivariate analyses and classification models were applied to clinical and -omic integrated datasets. In T1D patients and their siblings, Clostridiales and Dorea were increased and Dialister and Akkermansia were decreased compared to CTRL, while in T1D, Lachnospiraceae were higher and Collinsella was lower, compared to siblings and CTRL. Higher levels of isobutyrate, malonate, Clostridium, Enterobacteriaceae, Clostridiales, Bacteroidales, were associated to T1D compared to CTRL. Patients with higher anti-GAD levels showed low abundances of Roseburia, Faecalibacterium and Alistipes and those with normal blood pH and low serum HbA1c levels showed high levels of purine and pyrimidine intermediates. We detected specific gut microbiota profiles linked to both T1D at the onset and to diabetes familiarity. The presence of specific microbial and metabolic profiles in gut linked to anti-GAD levels and to blood acidosis can be considered as predictive biomarker associated progression and severity of T1D.

Pseudohypobicarbonatemia in a patient with amyloidosis.

We report a case of a patient who had critically low serum bicarbonate (HCO3 -) levels ranging from 8 to 11mmol/L on repeated venous measurements using an enzymatic/photometric assay. This prompted hospitalization and treatment with intravenous sodium bicarbonate (NaHCO3) followed by oral NaHCO3. He was evaluated for potential causes of high anion gap metabolic acidosis without any etiology found. He continued to have low serum HCO3 - levels despite maintenance oral NaHCO3 therapy and was referred for a second opinion where further laboratory work was pursued. An arterial blood gas was obtained, which revealed normal whole blood pH and HCO3 - levels. A different enzymatic/photometric assay revealed a normal serum HCO3 - level at 21mmol/L. Additional workup revealed paraproteinemia, which was thought to interfere with the enzymatic process by which his serum HCO3 - was measured, resulting in erroneous values.

Hyperglycemic hyperosmolar state in children: a case series

Background: Hyperglycemic hyperosmolar state (HHS) is a life-threatening rare acute complication of diabetes mellitus (DM). The condition should be distinguished from diabetic ketoacidosis (DKA) as the management differs significantly. HHS is classically associated with type 2 DM, but it has been increasingly reported in type I DM as well. The literature regarding HHS in children is still sparse. The management of HHS in children is extrapolated from the adult study. Cases: The first case was male 5 years old, and the second case was female 15 years old. Both cases were typed 1 DM patient. The first case was newly diagnosed. Both of the patients came with general weakness, mild dehydration, overly high blood sugar, normal blood pH, hypocalcemia, glucosuria and only mild ketonuria. In the second case develop, both patients were rehydrated, given insulin and discharged in 7-10 days without any sequelae. Conclusion: These case series emphasize the importance of recognizing HHS and differ it from DKA. These two cases prove that HHS is increasingly reported in children with clinical symptoms resembling DKA. It is also proven that with early diagnosis and correct management, children with HHS can be discharged home without any sequelae.

Nanoantidote for repression of acidosis pH promoting COVID-19 infection.

Acidosis, such as respiratory acidosis and metabolic acidosis, can be induced by coronavirus disease 2019 (COVID‐19) infection and is associated with increased mortality in critically ill COVID‐19 patients. It remains unclear whether acidosis further promotes SARS‐CoV‐2 infection in patients, making virus removal difficult. For antacid therapy, sodium bicarbonate poses great risks caused by sodium overload, bicarbonate side effects, and hypocalcemia. Therefore, new antacid antidote is urgently needed. Our study showed that an acidosis‐related pH of 6.8 increases SARS‐CoV‐2 receptor angiotensin‐converting enzyme 2 (ACE2) expression on the cell membrane by regulating intracellular microfilament polymerization, promoting SARS‐CoV‐2 pseudovirus infection. Based on this, we synthesized polyglutamic acid‐PEG materials, used complexation of calcium ions and carboxyl groups to form the core, and adopted biomineralization methods to form a calcium carbonate nanoparticles (CaCO3‐NPs) nanoantidote to neutralize excess hydrogen ions (H+), and restored the pH from 6.8 to approximately 7.4 (normal blood pH). CaCO3‐NPs effectively prevented the heightened SARS‐CoV‐2 infection efficiency due to pH 6.8. Our study reveals that acidosis‐related pH promotes SARS‐CoV‐2 infection, which suggests the existence of a positive feedback loop in which SARS‐CoV‐2 infection‐induced acidosis enhances SARS‐CoV‐2 infection. Therefore, antacid therapy for acidosis COVID‐19 patients is necessary. CaCO3‐NPs may become an effective antacid nanoantidote superior to sodium bicarbonate.

Non‐acidotic hypercapnia limits the loss of diaphragm force at single fiber level in mechanically ventilated rats for 5 days

The diaphragm loss of function resulting from Mechanical Ventilation (MV) in Intensive Care Unit (ICU) patients has been termed “Ventilator Induced Diaphragmatic Dysfunction” (VIDD) and is characterized by a rapid and progressive loss of diaphragm muscle mass and function. Hypercapnia is a frequent condition in mechanically ventilated ICU patients and accepted as “permissive hypercapnia” in ARDS. There are numerous negative effects of this gas imbalance on different tissues and their functions are well known, whereas the positive effects are still poorly understood. Acute hypercapnic exposure has shown benefit to in vivo diaphragm function in porcine and rat ICU models, however our understanding of the effects of longer‐term ventilation and the downstream signaling are less known. Here, we hypothesize that normoxic non acidotic hypercapnia would augment diaphragm muscle function during development of VIDD. Adult female Sprague‐Dawley rats were deeply sedated, pharmacologically paralyzed, hydrated, nourished and controlled mechanical ventilated (CMV) for 5 days in normoxic‐normocapnic or normoxic, hypercapnic conditions. Hypercapnic conditions maintained EtCO2 between 55 and 70 mmHg for the duration of the experiment ensuring normal arterial blood pH (7.37 – 7.43), thus they were non‐acidotic hypercapnic conditions. This unique experimental rat model is more representative of the prolonged nature and effects of VIDD and thus provides clinically relevant assessment of hypercapnic treatment efficacy. Diaphragm muscles were dissected and prepared for contractile function assessment and downstream signalling assessed at the gene and protein level.Our results show that: 1) cross sectional area (CSA) was decreased by 40% following normocapnic CMV when compared with CTR (p&lt; 0.001), which was unaltered by hypercapnia treatment; 2) Specific force (SF; force normalised to CSA) was decreased to 58% of CTR following normocapnic CMV (p&lt; 0.001). Non‐acidotic hypercapnia increased SF by 15% when compared with normocapnic rats (p&lt; 0.05); 3) Muscle E3 ligases Murf1 and Atrogin‐1 protein expression is unchanged following 5 days of CMV, irrespective of C02 conditions. LC3B is a known marker for autophagy, with LC3B II:I ratio signifying activation. Following 5 days normocapnic CMV LC3B II:I ratio (p&lt; 0.05) was reduced by 70% in diaphragm muscle. Non‐acidotic hypercapnic conditions failed to alter the activation of LC3B or these muscle degradation pathways; 4) Non‐acidotic hypercapnic conditions however increased TNFα and Interleukin 1β transcript expression in the diaphragm when compared with normocapnic CMV and CTR groups; 5) Non‐acidotic hypercapnic conditions increased stability of respiratory peak pressure, peripheral oxygenation and perfusion, hemodynamic conditions, thus promoting the benefits of non‐acidotic hypercapnic conditions.Our results suggest that non‐acidotic hypercapnic conditions have beneficial effects on single fibre diaphragm function irrespective of significant increase in muscle inflammation in non‐septic animals. This, combined with the positive respiratory and hemodynamic effects, encourage further study of the therapeutic potential of CO2 in ICU contexts.

Sickle cell disease and COVID-19 in pregnant women

IntroductionThe effect of coronavirus disease (COVID-19) on pregnancy outcome in women with sickle cell disease (SCD) is unknown. ObjectivesTo analyze the severity of the SARS-CoV-2 infection in pregnant women with SCD and its impact on pregnancy. MethodsThis retrospective cohort study included SCD pregnant women tested positive for COVID-19 between March 2020 – February 2021. The primary endpoint was the severity of the COVID-19 infection. Secondary endpoints were pregnancy complications and fetal outcomes. ResultsDuring the study period among 82 pregnant women with SCD, 8 have presented symptoms suggestive of COVID-19 and were tested positive. A common mild clinical presentation was observed in 6 women (75%), one woman was asymptomatic and one required oxygen. The latter was admitted to the Intensive Care Unit and a cesarean section was performed in the context of an ongoing vaso-occlusive crisis and acute chest syndrome together with incidental preeclampsia. Labor was induced in another patient who developed a vaso-occlusive crisis after COVID-19 remission. Fetal outcomes were good with an average Apgar score of 10 and normal umbilical blood pH at birth. Two newborns were small-for-gestational-age as expected on the ultrasound follow-up before occurrence of COVID-19. ConclusionCOVID-19 infection in our population of pregnant women with SCD had typical presentation and rarely triggered a sickle cell crisis or other complications. Fetal outcomes were good and did not seem to be directly influenced by the SARS-CoV-2 virus. Further studies are required to confirm these observations as compared to the population of women with SCD without COVID-19 infection.

Effects of Mean Artery Pressure and Blood pH on Survival Rate of Patients with Acute Kidney Injury Combined with Acute Hypoxic Respiratory Failure: A Retrospective Study.

Background and Objectives: In the intensive care unit (ICU), renal failure and respiratory failure are two of the most common organ failures in patients with systemic inflammatory response syndrome (SIRS). These clinical symptoms usually result from sepsis, trauma, hypermetabolism or shock. If this syndrome is caused by septic shock, the Surviving Sepsis Campaign Bundle suggests that vasopressin be given to maintain mean arterial pressure (MAP) > 65 mmHg if the patient is hypotensive after fluid resuscitation. Nevertheless, it is important to note that some studies found an effect of various mean arterial pressures on organ function; for example, a MAP of less than 75 mmHg was associated with the risk of acute kidney injury (AKI). However, no published study has evaluated the risk factors of mortality in the subgroup of acute kidney injury with respiratory failure, and little is known of the impact of general risk factors that may increase the mortality rate. Materials and Methods: The objective of this study was to determine the risk factors that might directly affect survival in critically ill patients with multiple organ failure in this subgroup. We retrospectively constructed a cohort study of patients who were admitted to the ICUs, including medical, surgical, and neurological, over 24 months (2015.1 to 2016.12) at Chiayi Chang Gung Memorial Hospital. We only considered patients who met the criteria of acute renal injury according to the Acute Kidney Injury Network (AKIN) and were undergoing mechanical ventilator support due to acute respiratory failure at admission. Results: Data showed that the overall ICU and hospital mortality rate was 63.5%. The most common cause of ICU admission in this cohort study was cardiovascular disease (31.7%) followed by respiratory disease (28.6%). Most patients (73%) suffered sepsis during their ICU admission and the mean length of hospital stay was 24.32 ± 25.73 days. In general, the factors independently associated with in-hospital mortality were lactate > 51.8 mg/dL, MAP ≤ 77.16 mmHg, and pH ≤ 7.22. The risk of in-patient mortality was analyzed using a multivariable Cox regression survival model. Adjusting for other covariates, MAP ≤ 77.16 mmHg was associated with higher probability of in-hospital death [OR = 3.06 (1.374–6.853), p = 0.006]. The other independent outcome predictor of mortality was pH ≤ 7.22 [OR = 2.40 (1.122–5.147), p = 0.024]. Kaplan-Meier survival curves were calculated and the log rank statistic was highly significant. Conclusions: Acute kidney injury combined with respiratory failure is associated with high mortality. High mean arterial pressure and normal blood pH might improve these outcomes. Therefore, the acid–base status and MAP should be considered when attempting to predict outcome. Moreover, the blood pressure targets for acute kidney injury in critical care should not be similar to those recommended for the general population and might prevent mortality.

Assessment of Acid-Base Status: Beyond Serum Bicarbonate.

Maintenance of normal blood pH is critical for cellular function. Yet, blood pH is uncommonly measured in the outpatient setting. Instead, serum [total CO2] ([TCO2]) is used to screen for acid-base disturbances, the argument being that both metabolic and respiratory disorders are generally

The Role of Acidosis in the Pathogenesis of Severe Forms of COVID-19.

Simple SummaryRecently, several studies have shown that acidosis, which is increased acidity in the blood and other body tissues, is often associated with severe COVID-19. In this article, we look at the mechanisms and consequences of acidosis that can lead to an exacerbation of COVID-19. We want to draw the attention of readers to the threshold values of such disease characteristics as hypoxia and acidosis, which are associated with a sharp deterioration in the patient’s condition. Hypoxia and acidosis mutually reinforce each other according to the principle of a vicious cycle (that is, they are involved in a system of positive feedbacks). Elevated blood lactate (lactic acid) levels are associated with poor clinical outcomes in COVID patients. As a practical recommendation, we propose to pay more attention to the prevention of acidosis, including in the early stages of the disease, when the adjustment of homeostasis requires less effort and is less risky.COVID-19 has specific characteristics that distinguish this disease from many other infections. We suggest that the pathogenesis of severe forms of COVID-19 can be associated with acidosis. This review article discusses several mechanisms potentially linking the damaging effects of COVID-19 with acidosis and shows the existence of a vicious cycle between the development of hypoxia and acidosis in COVID-19 patients. At the early stages of the disease, inflammation, difficulty in gas exchange in the lungs and thrombosis collectively contribute to the onset of acidosis. In accordance with the Verigo-Bohr effect, a decrease in blood pH leads to a decrease in oxygen saturation, which contributes to the exacerbation of acidosis and results in a deterioration of the patient’s condition. A decrease in pH can also cause conformational changes in the S-protein of the virus and thus lead to a decrease in the affinity and avidity of protective antibodies. Hypoxia and acidosis lead to dysregulation of the immune system and multidirectional pro- and anti-inflammatory reactions, resulting in the development of a “cytokine storm”. In this review, we highlight the potential importance of supporting normal blood pH as an approach to COVID-19 therapy.

Effect of an ionic antineoplastic agent Cytoreg on blood chemistry in a Wistar rat model.

Cytoreg is an ionic therapeutic agent comprising a mixture of hydrochloric, sulfuric, phosphoric, hydrofluoric, oxalic, and citric acids. In diluted form, it has demonstrated efficacy against human cancers in vitro and in vivo. Although Cytoreg is well tolerated in mice, rats, rabbits, and dogs by oral and intravenous administration, its mechanism of action is not documented. The acidic nature of Cytoreg could potentially disrupt the pH and levels of ions and dissolved gases in the blood. Here, we report the effects of the intravenous administration of Cytoreg on the arterial pH, oxygen and carbon dioxide pressures, and bicarbonate, sodium, potassium, and chloride concentrations. Our results demonstrate that Cytoreg does not disturb the normal blood pH, ion levels, or carbon dioxide content, but increases oxygen levels in rats. These data are consistent with the excellent tolerability of intravenous Cytoreg observed in rabbits, and dogs. The study was approved by the Bioethics Committee of the University of the Andes, Venezuela (CEBIOULA) (approval No. 125) on November 3, 2019.

Association between HOMA-IR with ketoacidosis and lipid profile markers in diabetic nephropathy patients

&nbsp;&nbsp; The study designed to study the relationship between the homeostatic model assessment of insulin resistance (HOMA-IR) with ketoacidosis markers and hyperlipidemia in patients with non-insulin-dependent diabetes mellitus (NIDDM) and chronic kidney disease at end-stage renal disease (ESRD). Disturbance of the mechanisms which maintain normal blood pH and lipid profiles is a defining feature of chronic metabolic diseases such as diabetes and kidney failure. The present research included 90 patients and 30 healthy subjects. Serum insulin, fasting blood sugar (FBS), glycated hemoglobin % (HbA1c %) and HOMA-IR levels, lipid profile parameters and ketoacidosis markers were estimated in all groups. Statistical analysis showed that high HOMA-IR was significantly associated with lipid profiles and ketoacidosis markers in patients' groups when compared with control. Receiver operating characteristic (ROC) curve analysis investigated HOMA-IR as a significant risk factor for diabetic nephropathy (DN) in ESRD patients. The present finding regarding ROC curve analysis observed that IR is dependently associated with ketoacidosis and lipid profile abnormalities in NIDDM, ESRD and DN patients. &nbsp;Also, the study suggested HOMA-IR as a consequence and risk factor in DN at ESRD.

Antimalarial Quinacrine and Chloroquine Lose Their Activity by Decreasing Cationic Amphiphilic Structure with a Slight Decrease in pH.

Quinacrine (QC) and chloroquine (CQ) have antimicrobial and antiviral activities as well as antimalarial activity, although the mechanisms remain unknown. QC increased the antimicrobial activity against yeast exponentially with a pH-dependent increase in the cationic amphiphilic drug (CAD) structure. CAD-QC localized in the yeast membranes and induced glucose starvation by noncompetitively inhibiting glucose uptake as antipsychotic chlorpromazine (CPZ) did. An exponential increase in antimicrobial activity with pH-dependent CAD formation was also observed for CQ, indicating that the CAD structure is crucial for its pharmacological activity. A decrease in CAD structure with a slight decrease in pH from 7.4 greatly reduced their effects; namely, these drugs would inefficiently act on falciparum malaria and COVID-19 pneumonia patients with acidosis, resulting in resistance. The decrease in CAD structure at physiological pH was not observed for quinine, primaquine, or mefloquine. Therefore, restoring the normal blood pH or using pH-insensitive quinoline drugs might be effective for these infectious diseases with acidosis.

Sialoglycan recognition is a common connection linking acidosis, zinc, and HMGB1 in sepsis

Blood pH is tightly maintained between 7.35 and 7.45, and acidosis (pH <7.3) indicates poor prognosis in sepsis, wherein lactic acid from anoxic tissues overwhelms the buffering capacity of blood. Poor sepsis prognosis is also associated with low zinc levels and the release of High mobility group box 1 (HMGB1) from activated and/or necrotic cells. HMGB1 added to whole blood at physiological pH did not bind leukocyte receptors, but lowering pH with lactic acid to mimic sepsis conditions allowed binding, implying the presence of natural inhibitor(s) preventing binding at normal pH. Testing micromolar concentrations of divalent cations showed that zinc supported the robust binding of sialylated glycoproteins with HMGB1. Further characterizing HMGB1 as a sialic acid-binding lectin, we found that optimal binding takes place at normal blood pH and is markedly reduced when pH is adjusted with lactic acid to levels found in sepsis. Glycan array studies confirmed the binding of HMGB1 to sialylated glycan sequences typically found on plasma glycoproteins, with binding again being dependent on zinc and normal blood pH. Thus, HMGB1-mediated hyperactivation of innate immunity in sepsis requires acidosis, and micromolar zinc concentrations are protective. We suggest that the potent inflammatory effects of HMGB1 are kept in check via sequestration by plasma sialoglycoproteins at physiological pH and triggered when pH and zinc levels fall in late stages of sepsis. Current clinical trials independently studying zinc supplementation, HMGB1 inhibition, or pH normalization may be more successful if these approaches are combined and perhaps supplemented by infusions of heavily sialylated molecules.

Neonatal congenital hyperinsulinism in Indonesia

Congenital hyperinsulinism (CHI) is resulted from dysregulated insulin secretion from hyperplastic and hyperactive but apparently normally structured β-cells islet. Principal management is maintaining normal blood glucose level by giving high GIR and pharmacological therapy. Surgery is chosen when CHI is unresponsive to pharmacological treatment. A 3-days-old girl was admitted to Sanglah Hospital, with a complaint of lethargic, refused to drink, seizure, weak tonus. The patient had a very low blood glucose level, normal lactate level, normal blood pH, high fasting insulin and C-Peptide level, normal cortisol, normal growth hormone, normal TSHs, and FT4 level, no ketonuria, no glucosuria, and no proteinuria. An abdominal CT scan showed diffuse dilatation of the caput, corpus, and tail of the pancreas without pancreatic duct dilatation. The patient was treated with Hydrocortisone, Octreotide, Nifedipine, and a high glucose infusion rate. The patient was undergone subtotal pancreatectomy and only remained 22% from the previous size. Histopathologic examination revealed serous acini zymogenic cells that were arranged in lobules, hyperplastic of the Langerhans islands, and cell within Langerhans islands. Post-surgery condition, she had controlled blood glucose, good drink tolerance, without a recurrent seizure. CHI is a rare disease and differential diagnosis of persistent hypoglycemia in the infant. Comprehensive and multidisciplinary management is required for a better outcome.

A pH-Sensitive Polymer for Cancer Targeting Prepared by One-Step Modulation of Functional Side Groups

Nanocarriers with pH-sensitive functionality are of great interest in the development of pH-dependent drug release compounds in acidic tumor microenvironments. A new polyelectrolyte block copolymer, poly[(benzyl-L-aspartate)-co-(N-(3-aminopropyl) imidazole-L-aspartamide)]-poly(ethylene glycol) (PABI-PEG), was prepared by one-step modulation to produce pH-sensitive nanocarriers. PABI-PEG formed a stable nanocarrier at pH values above 7.4 and was destabilized in acidic conditions (pH 6.5) through the protonation of the imidazole groups. Docetaxel loaded micelle (DLM) exhibited pH-dependent drug release through structural conversion due to the protonation of the imidazole groups on the PABI block. The critically low micelle concentration of PABI-PEG at physiological pH and the pH-dependent drug release would result to high stability and restrict drug loss during systemic circulation which may lower the toxicity of normal tissue to physiological pH. Additionally, the extracellular tumor pH (<7.0) and early endosomal pH (<6.5) environments triggered the disintegration of micelles, producing higher drug release compared to other normal tissues and blood (pH 7.4). Therefore, PABI-PEG may be a pHsensitive drug delivery method for cancer chemotherapy.

PENGARUH PEMBERIAN TERAPI OKSIGEN DENGAN MENGGUNAKAN NON-REBREATHING MASK (NRM) TERHADAP NILAI TEKANAN PARSIAL CO2 (PaCO2) PADA PASIEN CEDERA KEPALA SEDANG (MODERATE HEAD INJURY) DI RUANG INTENSIVE CARE UNIT (ICU) RSUP H ADAM MALIK MEDAN TAHUN 2016

Head injury is any cases that caused high disability and mortallity rate. In neurology, head injury occupies the first squence and become the main of health problem to most youth, health and productive peoples. The treatment of head injury treatment is to prevent damage of brain cells by adequate oxygenation. The objective of the research was to find out the influence of giving oxygent therapy by using non-rebreathing mask (NRM) towards changing of partial pressure CO2 (PaCO2) value to head injury patients in ICU room of H. Adam Malik Hospital Medan. The research used the quasi experiment method with time series design. The samples were 10 respondents, taken by purpossive sampling technique. The instrument of the research was observation sheet. The result of the research showed that before given the oxygent therapy by using nonrebreathing mask (NRM), 5 respondents (50%) had normal blood pH value, 6 respondents (60%) had low blood HCO3- value, and 6 respondents (60%) had normal blood PaCO2 value. After given oxygent therapy found that 5 respondents (50%) had low blood pH value, 6 respondents (60%) had low blood HCO3- value, and 7 respondents (70%) had low blood PaCO2 value. The result of statistic analyze with T-Test was found significant influence of changing PaCO2 value with p value = 0,000 (p&lt;0,05). The reduction of PaCO2 value is followed by increasing of blood pH value and reduction of blood HCO3- value. Using of non-rebreathing mask (NRM) is only effective for head injury patients with high blood PaCO2.

Polymeric micelles with photo-activated proton release behavior for enhanced tumor extracellular pH targeting and drug release

The extracellular pH (6.5–7.2) of most tumors varies only slightly from those of the normal tissues and blood (pH 7.4). For enhanced tumor extracellular pH targeting, Polymeric micelles (PM) based on 1-pyrenemethanol-modified carboxymethyl chitosan conjugate with succinyl linkage (PCMC) were constructed to regulate tumor extracellular pH. TEM observation showed that the micelles had a core–shell structure with an average diameter of 210±10.7nm. Dynamic light scattering studies indicated that the micelles had good in vitro stability. However, upon exposure to UV stimuli, the micelles weredisrupted and accompanied by proton release, which could trigger the aggregation of non-irradiated micelles at pH 6.0. The UV intensity and irradiation time showed an obvious influence on theproton release. The proton release mechanism may be attributed to the photosolvolysis of the ester bond linked to the pyrenemethyl groups in the polymeric side chains, which was proved by UV–Vis and 1H NMR. Paclitaxel (PTX) was entrapped into the core of micelles as a model drug, which only showed an accumulative release rate of 3.5% within 12h at pH 7.4. However, at pH 6.8 with UV irradiation (365nm, 500mWcm−2) for 4min and subsequently by mixing with an aliquot of non-irradiated drug-loaded sample, an enhanced drug release and significant inhibition rate against HeLa cells were observed. The study provided a new strategy for the design of tumor extracellular pH targeted nanocarriers for drug delivery.

NBCe1‐B/C Knockout Mice Exhibit Signs Associated with Proximal Renal Tubular Acidosis

The SLC4A4 gene encodes three major variants of the electrogenic Na+/HCO3− cotransporter NBCe1: NBCe1‐A, ‐B, and ‐C. NBCe1‐A is expressed in the kidney and contributes to blood pH homeostasis. NBCe1‐B and ‐C are expressed in a diverse array of non‐renal cells and contribute to intracellular pH homeostasis and fluid secretion. Individuals with NBCe1 mutations exhibit proximal renal tubular acidosis (pRTA). Disease signs include low blood pH, diverse ocular abnormalities, and poor dentition. Current treatments for pRTA focus solely on correcting blood pH. Thus it is of interest to determine which signs of pRTA are secondary to the acidosis (due to NBCe1‐A loss) and which are a primary consequence of NBCe1‐B/C loss.There are two previously reported mouse models of the disease: [1] Mice lacking NBCe1 (all variants) that exhibit low blood pH, corneal edema, weak tooth enamel, and impacted intestines; these do not survive beyond 25 days and [2] Mice lacking NBCe1‐A (but expressing NBCe1‐B/C) that exhibit low blood pH and elevated intraocular pressure, but otherwise thrive normally. We have generated a line of mice that, by CRISPR/Cas9 disruption of a common exon, lack NBCe1‐B/C while maintaining expression of NBCe1‐A. These mice have a normal blood pH yet exhibit corneal edema, chalky incisors, and failure to thrive. Thus non‐renal forms of NBCe1 contribute directly to the signs of pRTA and these pathologies, unlikely to be addressed by alkali therapy, require supplemental treatment.Support or Funding InformationStart‐up funds from the Dean of the Jacobs School of Medicine and Biomedical Sciences and The Department of Physiology and Biophysics at the University at Buffalo