Sebaceous hyperplasia is a common disease in middle-aged adults. The lesions usually present as solitary or multiple yellowish tiny papules on the face. The areola, vulva and penis are rarely reported sites for this malady. There is no definitely successful treatment for sebaceous hyperplasia. A 35-year-old woman presented with a one-year-history of numerous asymptomatic tiny confluent papules arranged in yellowish plaques surrounding both nipples. Histologic examination showed multiple clustered sebaceous lobules around a centrally located, dilated sebaceous duct. The lesion was treated by applying dichloroacetic acid. After 6 weeks, the lesion had resolved leaving faint postinflammatory hypopigmentation. Herein, we report a rare case of areolar sebaceous hyperplasia that was treated with dichloroacetic acid.
Adult ; Dichloroacetic Acid ; Female ; Humans ; Hyperplasia ; Hypopigmentation ; Male ; Nipples ; Penis ; Vulva

BACKGROUND: Xanthelasma palpebrarum is the most common type of xanthoma. Due to its delicate location near the eye, treatment of xanthelasma palpebrarum is rather difficult. The treatment includes surgical excision, local treatment with chemicals, and various laser therapies. OBJECTIVE: This study was designed to review the various therapeutic modalities and to evaluate the efficacy and safety of bichloroacetic acid (BCA) for the treatment of xanthelasma palpebrarum. METHODS: Nine patients, with a total of 19 xanthelasma lesions, were treated with BCA. The efficacy and safety were assessed over a follow-up period of 6 to 24 months (average, 16 months). RESULTS: All lesions were grossly removed completely with a single treatment and the treatment was well-tolerated by patients. Erythema and oozing were observed in six patients but improved after two weeks' dressing. Xanthelasma palpebrarum recurred in three patients, but the mean size of the recurred lesions was smaller in comparison to the primary lesion. CONCLUSION: BCA is an effective and safe therapeutic modality for xanthelasma palpebrarum. Advantages include simplicity, cost-effectiveness, speed, safety and efficacy.
Bandages ; Dichloroacetic Acid* ; Erythema ; Follow-Up Studies ; Humans ; Laser Therapy ; Xanthomatosis

Metabolic aberrations in the form of altered flux through key metabolic pathways are the major hallmarks of several life-threatening malignancies including malignant gliomas. These adaptations play an important role in the enhancement of the survival and proliferation of gliomas at the expense of the surrounding normal/healthy tissues. Recent studies in the field of neurooncology have directly targeted the altered metabolic pathways of malignant tumor cells for the development of anti-cancer drugs. Aerobic glycolysis due to elevated production of lactate from pyruvate regardless of oxygen availability is a common metabolic alteration in most malignancies. Aerobic glycolysis offers survival advantages in addition to generating substrates such as fatty acids, amino acids and nucleotides required for the rapid proliferation of cells. This review outlines the role of pyruvate dehydrogenase kinase (PDK) in gliomas as an inhibitor of pyruvate dehydrogenase that catalyzes the oxidative decarboxylation of pyruvate. An in-depth investigation on the key metabolic enzyme PDK may provide a novel therapeutic approach for the treatment of malignant gliomas.
Amino Acids ; Decarboxylation ; Dichloroacetic Acid ; Fatty Acids ; Glioma* ; Glycolysis ; Lactic Acid ; Metabolic Networks and Pathways ; Nucleotides ; Oxidoreductases* ; Oxygen ; Phosphotransferases* ; Pyruvic Acid*

High extracellular glucose concentration was reported to suppress intracellular Ca2+ clearing through altered sarcoplasmic reticulum (SR) function. In the present study, we attempted to elucidate the effects of pyruvate and fatty acid on SR function and reveal the mechanistic link with glucose-induced SR dysfunction. For this purpose, SR Ca2+-uptake rate was measured in digitonin-permeabilized H9c2 cardiomyocytes cultured in various conditions. Exposure of these cells to 5 mM pyruvate for 2 days induced a significant suppression of SR Ca2+-uptake, which was comparable to the effects of high glucose. These effects were accompanied with decreased glucose utilization. However, pyruvate could not further suppress SR Ca2+-uptake in cells cultured in high glucose condition. Enhanced entry of pyruvate into mitochondria by dichloroacetate, an activator of pyruvate dehydrogenase complex, also induced suppression of SR Ca2+-uptake, indicating that mitochondrial uptake of pyruvate is required in the SR dysfunction induced by pyruvate or glucose. On the other hand, augmentation of fatty acid supply by adding 0.2 to 0.8 mM oleic acid resulted in a dose-dependent suppression of SR Ca2+-uptake. However, these effects were attenuated in high glucose-cultured cells, with no significant changes by oleic acid concentrations lower than 0.4 mM. These results demonstrate that (1) increased pyruvate oxidation is the key mechanism in the SR dysfunction observed in high glucose-cultured cardiomyocytes; (2) exogenous fatty acid also suppresses SR Ca2+-uptake, presumably through a mechanism shared by glucose.
Diabetic Cardiomyopathies* ; Dichloroacetic Acid ; Glucose ; Hand ; Mitochondria ; Myocytes, Cardiac* ; Oleic Acid ; Pyruvate Dehydrogenase Complex ; Pyruvic Acid* ; Sarcoplasmic Reticulum*

Glioblastoma multiforme (GBM) is the most common and aggressive form of brain tumors. GBMs, like other tumors, rely relatively less on mitochondrial oxidative phosphorylation (OXPHOS) and utilize more aerobic glycolysis, and this metabolic shift becomes augmented under hypoxia. In the present study, we investigated the physiological significance of altered glucose metabolism and hypoxic adaptation in the GBM cell line U251 and two newly established primary GBMs (GBM28 and GBM37). We found that these three GBMs exhibited differential growth rates under hypoxia compared to those under normoxia. Under normoxia, the basal expressions of HIF1α and the glycolysis-associated genes, PDK1, PDK3, and GLUT1, were relatively low in U251 and GBM28, while their basal expressions were high in GBM37. Under hypoxia, the expressions of these genes were enhanced further in all three GBMs. Treatment with dichloroacetate (DCA), an inhibitor of pyruvate dehydrogenase kinase (PDK), induced cell death in GBM28 and GBM37 maintained under normoxia, whereas DCA effects disappeared under hypoxia, suggesting that hypoxic adaptation dominated DCA effects in these GBMs. In contrast, the inhibition of HIF1α with chrysin suppressed the expression of PDK1, PDK3, and GLUT1 and markedly promoted cell death of all GBMs under both normoxia and hypoxia. Interestingly, however, GBMs treated with chrysin under hypoxia still sustained higher viability than those under normoxia, and chrysin and DCA co-treatment was unable to eliminate this hypoxia-dependent resistance. Together, these results suggest that hypoxic adaptation is critical for maintaining viability of GBMs, and targeting hypoxic adaptation can be an important treatment option for GBMs.
Anoxia ; Brain Neoplasms ; Cell Death* ; Cell Line ; Dichloroacetic Acid ; Glioblastoma* ; Glucose ; Glycolysis ; Metabolism ; Oxidative Phosphorylation ; Oxidoreductases ; Phosphotransferases ; Pyruvic Acid

Hyperglycemia has been reported to worsen the tolerance of the brain to ischemia, and it has therefore been recommended that patient undergoing neurosurgical procedures not receive glucose-containing solutions. Since ischemic events lead to increased lactate production and accumulation and hence neuronal damage, the present study was designed to test the effect of insulin-induced hypoglycemia and decreased lactate by 2-Deoxyglucose and Dichloroacetate on focal cerebral ischemia in rats. Although the pre and post-ischemic blood glucose levels of control group and Dichloroacetate group showed no change, the blood glucose level of 2-Deoxyglucose group showed a significant increase(p=0.001), and insulim group a significant decrease(p=0.004). The reducing effects on the infarct zone in these three treated groups were found with statistical significance. As compared with control group, the tissue lactate levels of treated groups were decreased in both infarct zone and border zone but these data did not show statistical significance. From these observations, it is suggested that reduction of lactate production and accumulation could be beneficial by affording neuronal protection in ischemic tissues.
Animals ; Blood Glucose ; Brain ; Brain Ischemia* ; Cerebral Infarction ; Deoxyglucose* ; Dichloroacetic Acid* ; Humans ; Hyperglycemia ; Hypoglycemia ; Insulin* ; Ischemia ; Lactic Acid ; Neurons ; Neurosurgical Procedures ; Rats*

OBJECTIVETo explore the effects of trichloroethylene (TCE) and its by-products (trichloroacetic acid, TCA; dichloroacetic acid, DCA) on the normal human peripheral blood lymphocyte and the role of DCA in dermatitis medicamentosa- like induced by trichloroethylene (DMLT).

METHODSLymphocyte was isolated from peripheral venous blood, and cytotoxicity of human lymphocytes treated with different concentrations (0.02 approximately 30.00 mmol/L) of DCA was determined at indicated times (2 h and 4 h) based on the MTS assay. Action of DCA on cell viability, membrane integrity was assessed by neutral red uptake (NRU) assay and lactate dehydrogenase (LDH) release test and measurement of superoxide dismutase (SOD) activity. Fluorescence quantitative reverse transcription polymerase chain reaction (FQ-RT-PCR) was employed for detection and quantization of the chemokine receptor CXCR2 and chemokine receptor CXCR3 mRNA in peripheral blood lymphocyte treated with different concentrations of DCA.

RESULTSDCA had a more vital effect on peripheral blood lymphocyte than TCE and TCA. A concentration-dependent release of LDH was observed at 4 h after cells were exposed to different doses of DCA (0.88, 1.75, 3.50 and 7.00 mmol/L) (P < 0.05), and DCA also caused an inhibition of SOD activity in a concentration-dependent manner (P < 0.05). The results of FQ- RT- PCR indicated that CXCR2 and CXCR3 mRNA were all over- expression. At 48 h after the DCA of 0.5 mmol/L and 10.00 mmol/L was used, CXCR2 and CXCR3 mRNA were 10.34, 5.66-fold and 19.43, 8.75-fold of those in the control group (P < 0.01).

CONCLUSIONDCA is of a great cytotoxicity and may be one of crucial evocators on DMLT.

Adolescent ; Cells, Cultured ; Dichloroacetic Acid ; toxicity ; Female ; Humans ; Lymphocytes ; drug effects ; metabolism ; Male ; Receptors, CXCR3 ; metabolism ; Receptors, Interleukin-8B ; metabolism ; Trichloroethylene ; toxicity ; Young Adult

Bichloroacetic acid(BCA), one of the chloroacetic acids, is an effective tissue cauterant when used in high concentration. In dermatologic surgery, BCA, in the form of 100% solution, has been used to treat xanthelasma, sebaceous hyperplasia, verrucae, hard and soft corn, seborrheic keratosis, ingrowing nail, cysts. The cauterization with BCA 100% solution can be used with a simpler technique than the surgical excision or electrical cauterization, without complicated appliance such as LASER generators, so the dermatologic surgical technique - BCA chemical cauterization, topical treatment - can be selected as a treatment of choice for many dermatologic conditions in outpatient offices. BCA destroys the barrier function of the epidermis and penetrates deeply through the papillary dermis and then creates the effect in the papillary dermis and reticular dermis. As a result, regeneration of new dermal collagens and a new epidermis occurs. This pharmacologic effect of BCA makes 100% solution of BCA to be used in the treatment of xanthelasma, pigmented nevi, acne scars with good clinical outcomes.
Acne Vulgaris ; Cautery ; Chloroacetates ; Cicatrix ; Collagen ; Dermatologic Surgical Procedures ; Dermis ; Dichloroacetic Acid ; Epidermis ; Humans ; Hyperplasia ; Keratosis, Seborrheic ; Nevus, Pigmented ; Outpatients ; Regeneration ; Skin Diseases* ; Skin* ; Warts ; Zea mays

Mammalian target of rapamycin (mTOR) controls cellular anabolism, and mTOR signaling is hyperactive in most cancer cells. As a result, inhibition of mTOR signaling benefits cancer patients. Rapamycin is a US Food and Drug Administration (FDA)-approved drug, a specific mTOR complex 1 (mTORC1) inhibitor, for the treatment of several different types of cancer. However, rapamycin is reported to inhibit cancer growth rather than induce apoptosis. Pyruvate dehydrogenase complex (PDHc) is the gatekeeper for mitochondrial pyruvate oxidation. PDHc inactivation has been observed in a number of cancer cells, and this alteration protects cancer cells from senescence and nicotinamide adenine dinucleotide (NAD^+‍) exhaustion. In this paper, we describe our finding that rapamycin treatment promotes pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) phosphorylation and leads to PDHc inactivation dependent on mTOR signaling inhibition in cells. This inactivation reduces the sensitivity of cancer cells' response to rapamycin. As a result, rebooting PDHc activity with dichloroacetic acid (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, promotes cancer cells' susceptibility to rapamycin treatment in vitro and in vivo.
Humans ; Sirolimus/pharmacology* ; Dichloroacetic Acid/pharmacology* ; Pyruvate Dehydrogenase Complex ; TOR Serine-Threonine Kinases ; Mechanistic Target of Rapamycin Complex 1 ; Neoplasms/drug therapy*

Since the mitochondrial pyruvate dehydrogenase complex (PDC) controls the rate of carbohydrate oxidation, impairment of PDC activity mediated by high-fat intake has been advocated as a causative factor for the skeletal muscle insulin resistance, metabolic syndrome, and the onset of type 2 diabetes (T2D). There are also situations where muscle insulin resistance can occur independently from high-fat dietary intake such as sepsis, inflammation, or drug administration though they all may share the same underlying mechanism, i.e., via activation of forkhead box family of transcription factors, and to a lower extent via peroxisome proliferator-activated receptors. The main feature of T2D is a chronic elevation in blood glucose levels. Chronic systemic hyperglycaemia is toxic and can lead to cellular dysfunction that may become irreversible over time due to deterioration of the pericyte cell's ability to provide vascular stability and control to endothelial proliferation. Therefore, it may not be surprising that T2D's complications are mainly macrovascular and microvascular related, i.e., neuropathy, retinopathy, nephropathy, coronary artery, and peripheral vascular diseases. However, life style intervention such as exercise, which is the most potent physiological activator of muscle PDC, along with pharmacological intervention such as administration of dichloroacetate or L-carnitine can prove to be viable strategies for treating muscle insulin resistance in obesity and T2D as they can potentially restore whole body glucose disposal.
Blood Glucose ; Carnitine ; Coronary Vessels ; Diabetes Mellitus, Type 2 ; Dichloroacetic Acid ; Diet, High-Fat ; Glucose ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Inflammation ; Insulin Resistance* ; Life Style ; Muscle, Skeletal ; Muscles ; Obesity ; Pericytes ; Peripheral Vascular Diseases ; Peroxisome Proliferator-Activated Receptors ; Pyruvate Dehydrogenase Complex* ; Sepsis ; Transcription Factors