Study on the correlation between maternal serum uric acid and foetal birth weight in Naqu, Tibet.

In high-altitude regions, low birth weight is mainly caused by hypoxia. We aimed to determine whether maternal serum uric acid (SUC) level was associated with decreased foetal birth weight. The relevant data of individual pregnant women who delivered between 37 and 40 weeks in the People's Hospital of Naqu City, Tibet were retrospectively collected. The correlation between maternal SUC and birth weight was examined using multivariate linear regression analysis and subgroup analysis. The results showed that there was a significant negative correlation between SUC and birth weight in pregnant women with proteinuria, female foetuses, and primiparas. Fitting smoothing curve analysis showed that there was a negative linear correlation between SUC and birth weight in primiparas and female foetuses. Maternal SUC is negatively associated with foetal birth weight in a single pregnancy with proteinuria, primipara, or female foetuses in the Naqu region of Tibet, China.IMPACT STATEMENTWhat is already known on this subject? Preeclampsia associated with hyperuricaemia can affect foetal birth weight, foetal birth weight in plains area is negatively correlated with maternal hyperuricaemia.What do the results of this study add? Maternal SUC was negatively correlated with foetal birth weight, especially in primipara, mothers with proteinuria, and pregnant girls.What are the implications of these findings for clinical practice and/or further research? The results suggest that attention should be paid to SUC in pregnant women, especially in primipara, mothers with proteinuria, and pregnant girls, in the prevention of low birth weight infants in Naqu Plateau area of Tibet.

Screening of genes involved in epithelial-mesenchymal transition and differential expression of complement-related genes induced by PAX2 in renal tubules.

AIM: The aim of the present study was to screen and verify downstream genes involved in the epithelial mesenchymal transition (EMT) induced by paired box 2 (PAX2) in NRK-52E cells. METHODS: NRK-52E cells were transfected with lentivirus carrying PAX2 gene or no-load virus respectively. Total RNA was isolated 72 h after transfection from PAX2-overexpressing cells and control cells. Isolated RNA was then hybridized with the Rat OneArray Plus expression profile chip. The chips were examined by Agilent 0.1 XDR to screen for differentially expressed genes, which were further analyzed to investigate complement-related genes as genes of interest. RESULTS: In NRK-52E cells, PAX2 overexpression promoted EMT followed by upregulation of 298 genes and downregulation of 293 genes. KEGG analysis indicated the differential expression of genes related to cytokines and their receptors, extracellular matrix (ECM), MAPKs, local adhesion, cancer, the complement cascade, and coagulation. Gene oncology analysis screened out genes related to molecular functions (e.g., hydrolase activity, phospholipase activity, components of the ECM) and biological processes (e.g., cell development, signal transduction, phylogeny), and cell components (e.g., cytoplasm, cell membrane, and ECM). Analysis of the complement system revealed upregulation of C3 and downregulation of CD55 and complement regulator factor H (CFH). CONCLUSION: PAX2 overexpression upregulates EMT in vitro and may regulate C3, CD55, and CFH.

[Influence of PAX2 gene silencing on renal interstitial fibrosis in rats].

OBJECTIVE: To investigate the influence of silencing PAX2 gene in vivo on epithelial-mesenchymal transition (EMT) of renal tubular cells in rats with renal interstitial fibrosis. METHODS: A total of 64 Wistar rats were anaesthetized, and unilateral ureteral obstruction (UUO) was performed to establish a rat model of renal interstitial fibrosis. The 64 rats were randomly divided into negative control and PAX2 gene silencing groups (n=32 each). The rats in the control group were transfected with 200 µL NC-siRNA-in vivo jetPEI(TM) solution. Those in the PAX2 gene silencing group were transfected with 200 µL PAX2-siRNA-in vivo jetPEI(TM) solution. Each group was further divided into 4 subgroups based on the post-transfection time (3, 5, 7 and 14 days after transfection), with 8 rats in each subgroup. Renal tissue samples were harvested in each group. Real-time PCR and Western blot were used to measure the mRNA and protein expression of PAX2 in the renal cortex, as well as the mRNA and protein expression of E-cadherin and α-SMA. RESULTS: Compared with the control group, the PAX2 gene silencing group showed significantly lower mRNA and protein expression of PAX2 (P<0.05). In the two groups, the mRNA and protein expression levels of E-cadherin were gradually reduced over the time of obstruction, while those of α-SMA gradually increased. At 14 days after transfection, the PAX2 gene silencing group had significantly higher mRNA and protein expression of E-cadherin but lower mRNA and protein expression of α-SMA compared with the control group (P<0.05). CONCLUSIONS: PAX2 gene silencing can significantly inhibit the process of EMT of renal tubular cells in rats with advanced fibrosis, suggesting that PAX2 gene silencing may have a therapeutic effect on renal interstitial fibrosis.

Due-window assignment scheduling with variable job processing times.

We consider a common due-window assignment scheduling problem jobs with variable job processing times on a single machine, where the processing time of a job is a function of its position in a sequence (i.e., learning effect) or its starting time (i.e., deteriorating effect). The problem is to determine the optimal due-windows, and the processing sequence simultaneously to minimize a cost function includes earliness, tardiness, the window location, window size, and weighted number of tardy jobs. We prove that the problem can be solved in polynomial time.

Interleukin-6 Downregulates the Expression of Vascular Endothelial-Cadherin and Increases Permeability in Renal Glomerular Endothelial Cells via the Trans-Signaling Pathway.

The pathogenesis of IgA nephropathy (IgAN) is still unknown, but reportedly, interleukin 6 (IL-6) is involved in this process. However, its role in damaging glomerular endothelial cells is still unclear. Therefore, in this study, to clarify the mechanism of the pathogenesis of IgAN, we investigated the effect of IL-6 on the permeability of glomerular endothelial cells. A rat model of IgAN was established, and the animals divided into two groups, namely, the normal and IgAN groups. Glomerular endothelial cell injury was evaluated via electron microscopy. Furthermore, IL-6-induced changes in the permeability of human renal glomerular endothelial cells (HRGECs) were measured via trans-endothelial resistance (TEER) measurements and fluorescein isothiocyanate-dextran fluorescence. Furthermore, vascular endothelial-cadherin (VE-cadherin) was overexpressed to clarify the effect of IL-6 on HRGEC permeability, and to determine the pathway by which it acts. The classical signaling pathway was blocked by silencing IL-6R and the trans-signaling pathway was blocked by sgp30Fc. In IgAN rats, electron microscopy showed glomerular endothelial cell damage and western blotting revealed a significant increase in IL-6 expression, while VE-cadherin expression decreased significantly in the renal tissues. IL-6/IL-6R stimulation also significantly increased the permeability of HRGECs (p < 0.05). This effect was significantly reduced by VE-cadherin overexpression (p < 0.01). After IL-6R was silenced, IL-6/IL-6R still significantly reduced VE-cadherin expression and sgp30Fc blocked the trans-signaling pathway as well as the upregulation of IL-6/IL-6R-induced VE-cadherin expression. This suggests that IL-6 mainly acts via the trans-signaling pathway. IL-6 increased the permeability of HRGECs by decreasing the expression of VE-cadherin via the trans-signaling pathway.

Streptococcal pneumonia-associated hemolytic uremic syndrome treated by T-antibody-negative plasma exchange in children: Two case reports.

BACKGROUND: The occurrence of Streptococcus pneumoniae-associated hemolytic uremic syndrome (SP-HUS) is increasing. Thomsen-Friedenreich antigen activation is highly involved in the pathogenesis of SP-HUS, and T-antibody-negative plasma exchange (PE) may be effective in the treatment of severe cases of SP-HUS. CASE SUMMARY: We retrospectively reviewed two pediatric patients with SP-HUS. Both clinical features and laboratory examination results of the children were described. T-antibody-negative PE was performed in both cases. Both children made a full recovery after repeated PE and remained well at a 2 year follow-up. CONCLUSION: Streptococcal pneumonia continues to be an uncommon but important cause of HUS. The successful treatment of the presented cases suggests that T-antibody-negative PE may benefit patients with SP-HUS.

Huaier Extract Attenuates Acute Kidney Injury to Chronic Kidney Disease Transition by Inhibiting Endoplasmic Reticulum Stress and Apoptosis via miR-1271 Upregulation.

Endoplasmic reticulum stress (ERS) is strongly associated with acute kidney injury (AKI) to chronic kidney disease (CKD) transition. Huaier extract (HE) protects against kidney injury; albeit, the underlying mechanism is unknown. We hypothesized that HE reduces kidney injury by inhibiting ERS. In this study, using an AKI-CKD mouse model of ischemia-reperfusion injury (IRI), we evaluated the effect of HE on AKI-CKD transition. We also explored the underlying molecular mechanisms in this animal model and in the HK-2 human kidney cell line. The results showed that HE treatment improved the renal function, demonstrated by a significant decrease in serum creatinine levels after IRI. HE appreciably reduced the degree of kidney injury and fibrosis and restored the expression of the microRNA miR-1271 after IRI. Furthermore, HE reduced the expression of ERS markers glucose-regulated protein 78 (GRP78) and C/EBP homologous protein (CHOP) and inhibited apoptosis in the IRI group. This in vivo effect was supported by in vitro results in which HE inhibited apoptosis and decreased the expression of CHOP and GRP78 induced by ERS. We demonstrated that CHOP is a target of miR-1271. In conclusion, HE reduces kidney injury, probably by inhibiting apoptosis and decreasing the expression of GRP78 and CHOP via miR-1271 upregulation.

[Effects of glutamine on extracellular signal regulated kinase and p38MAPK expression in the kidney in young rats with endotoxemia].

OBJECTIVE: Glutamine has protective effects against renal injuries. This study was designed to explore the possible mechanism underlying the protections by examining the effects of glutamine on extracellular signal regulated kinase (ERK) and p38MAPK expression in the kidney in rats with endotoxemia. METHODS: One hundred and twenty-one 18-day-old Wistar rats were randomly injected with LPS (4 mg/kg; n=55), LPS (4 mg/kg)+glutamine (1 mL/kg) (n=55), or normal saline (control group; n=11). The two LPS groups were subdivided into five groups sacrificed at 2, 4, 6, 24 and 72 hrs after administration (n=11 each). ERK-2 and p38MAPK mRNA and protein expression in the kidney were measured by RT-PCR and immunohistochemistry. RESULTS: Compared to the control group, the mRNA and protein expression of both ERK-2 and p38MAPK in the LPS group significantly increased 2, 4, 6, 24 and 72 hrs after administration (P<0.01), and reached a peak at 6 hrs (P<0.01). In the LPS+glutamine group, the trend of ERK-2 and p38MAPK expression was similar to the LPS group but their expression levels were significantly lower than those in the LPS group at all time points (P<0.05 or 0.01). CONCLUSIONS: Both ERK-2 and p38MAPK expression increased in young rats with LPS-induced endotoxemia. Glutamine alleviates renal injuries possibly by decreasing the expression of both.

Effects of Huaiqihuang Granules Adjuvant Therapy in Children with Primary Nephrotic Syndrome.

OBJECTIVE: This study aims to observe the curative effect of Huaiqihuang Granules adjuvant therapy on primary nephrotic syndrome (PNS). METHODS: A total of 112 children with PNS were randomly divided into three groups, and changes in serum inflammatory cytokines, interleukin, lymphocyte subsets and immunoglobulin were observed. RESULTS: Before treatment, IL-18, TNF-α, CD8+ increased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells decreased. After Huaiqihuang Granules treatment, IL-18, TNF-α, CD8+ decreased, while IL-10, CD4+, NK cells, IgA, IgG and Foxp3+Treg cells increased. CONCLUSION: Functions of cell immunity and humoral immunity in PNS patients before treatment were suppressed and disordered. Huaiqihuang granules can play a role in immunoregulation, with slight side reactions.

[A prospective multicenter clinical control trial on treatment of refractory nephrotic syndrome with mycophenolate mofetil in children].

OBJECTIVE: To evaluate the efficacy and safety of mycophenolate mofetil (MMF) plus prednisone on refractory nephrotic syndrome (RNS) in children. METHODS: One hundred and forty-two children with RNS from ten clinical trial centers were divided into two groups: MMF (n=87) and control (n=55). The MMF group patients were administered with oral MMF (30-40 mg/kg daily) for at least 6 months. Afterwards the patients who responded to MMF received another 6 months MMF treatment at a dosage of 10-20 mg/kg daily. The controls were treated with pulse intravenous infusion of cyclophosphamide (CTX) (10 mg/kg daily) for 2 days every 2 weeks for 3 months. Then CTX was administered at a dosage of 500 mg/m2 once a month 4, 7 and 10 months after treatment. While the patients received MMF or CTX treatment, they were treated with oral prednisone (0.5-1 mg/kg daily) for 2 to 3 months, and then the dosage of prednisone was gradually reduced. Urinary protein, liver and renal functions, and side effects of drugs were examined at regular intervals for one year. RESULTS: Of the 87 patients, 58 achieved complete remission, 16 achieved partial remission, 9 achieved early remission and 4 had no response to treatment. In the control group, 35 achieved complete remission, 9 achieved partial remission, 1 achieved early remission and 10 had no response to treatment. The total remission rate in the MMF group (95.4%) was significantly higher than that in the control group (81.8%) (P<0.01). After treatment 67 patients (65.4%) in the MMF group had negative proteinuria compared with 36 patients (65.4%) in the control group (P>0.05). MMF was found to be more effective in reducing proteinuria, and improving hypoproteinemia, oliguria, hyperlipemia, and edema than CTX. MMF was better tolerated with lower incidences of adverse reactions than CTX. CONCLUSIONS: The combined therapy of MMF and prednisone is more effective and tolerable than pulse intravenous infusion of CTX for treatment of RNS in children.

Preoperative and postoperative medical therapies for chronic rhinosinusitis: National surveys among Chinese otolaryngologists.

OBJECTIVE: The aim of this study was to evaluate clinical practice patterns of preoperative and postoperative medical therapies immediately surrounding sinus surgery for chronic rhinosinusitis (CRS) by Chinese otolaryngologists. METHODS: Two anonymous web-based surveys of preoperative and postoperative medical therapies were performed. These surveys assessed the frequency of prescription of oral corticosteroids, intranasal corticosteroid sprays, oral antibiotics, nasal saline irrigation, oral antihistamines, nasal antihistamines, anti-leukotriene agents, topical decongestants and oral mucolytics. RESULTS: A total of 304 (17.5%) preoperative and 143 (23.5%) postoperative questionnaires were completed and returned. Seventy-eight percent, 63% and 56% of respondents used preoperative intranasal corticosteroid sprays, oral antibiotics and oral mucolytics "always or often", respectively. Ninety-four percent, 93%, 72% and 69% of respondents used postoperative intranasal corticosteroid sprays, nasal saline irrigation, oral antibiotics and oral mucolytics "always or often", respectively. Oral antihistamines, nasal antihistamines, anti-leukotrienes and topical decongestants were not commonly used preoperatively or postoperatively. CONCLUSIONS: Our study demonstrated that current practice patterns of preoperative medical therapies among otolaryngologists are not uniformly based on evidence-based outcomes research. Postoperative oral antibiotics, intranasal corticosteroid sprays, nasal saline irrigation and oral mucolytics are commonly used by a majority of Chinese otolaryngologist for CRS. Practice patterns of postoperative medical therapy reflect recent guidelines.

Association of AKT1 gene polymorphisms with sporadic Parkinson's disease in Chinese Han population.

Genetic variants of AKT1 have been shown to influence brain function of Parkinson's disease (PD) patients, and in this paper our aim is to investigate the association between the three single-nucleotide polymorphisms (rs2498799; rs2494732; rs1130214) and PD in Han Chinese. 413 Han Chinese PD patients and 450 healthy age and gender-matched controls were genotyped using the Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP) method. Both the patient and control groups show similar genotype frequencies at the three loci: rs2498799, rs2494732 and rs1130214. We are able to identify a significant difference in the frequencies of genotype (p=0.019) and G allele (OR=0.764, 95% CI=0.587-0.995, p=0.045) both at rs2498799 between the patient and control groups. Furthermore, the association of subjects with GG genotypes versus those with GA+AA genotype remain significant after adjusting for age in the Han Chinese female cohort (OR=0.538, 95%CI=0.345-0.841, p=0.006), which is especially evident in the late-onset cohort (OR=0.521, 95%CI=0.309-0.877, p=0.012). In contrast, allele frequencies at rs2494732 and rs1130214 were similar between patients and controls in all subgroup analyses. These results suggest that polymorphism of AKT1 locus is associated with risk of PD and that the G allele at rs2498799 may decrease the risk of PD in the North-eastern part of Han Chinese female population.

Effect of dexamethasone on nitric oxide synthase and Caspase-3 gene expressions in endotoxemia in neonate rat brain.

OBJECTIVE: To investigate the gene and protein expressions of three isoforms of nitric oxide synthase (NOS) and gene expression of Caspase-3, and effect of dexamethasone on them in neonatal rats with lipopolysaccharide (LPS)-induced endotoxemic brain damage. METHODS: Expressions of the three isoforms of NOS and caspase-3 mRNA in the brain were investigated by RT-PCR in postnatal 7-day Wistar rats with acute endotoxemia by intraperitoneal administration of LPS. Regional distributions of NOSs were examined by immunohistochemical technique. RESULTS: nNOS and Caspase-3 mRNA were obviously detected. eNOS mRNA was faintly expressed, but iNOS mRNA was undetectable in the control rat brain. The expressions of NOS mRNA of three isoforms were weak 2 h after LPS (5 mg/mg) delivery, peaked at 6 h, and thereafter, reduced gradually up to 24 h. The expression intensity was in the order of nNOS> iNOS> eNOS. Widespread nNOS, scattered eNOS distribution and negative iNOS were identified in the control rat brain and all isoforms of NOS could be induced by LPS which reached the apex at 24 h in the order of nNOS> iNOS> eNOS as detected by immunostaining. Although Caspase-3 mRNA could be found in all groups, DNA fragmentation was only seen at 6 h and 24 h. The expressions of NOS and Caspase-3 mRNA were inhibited in the rat brain when dexamethasone was administrated. CONCLUSION: LPS-induced NO production induces apoptosis of neurons through mechanism involving the Caspase-3 activation, which may play an important role in the pathogenesis of brain damage during endotoxemia, and neuro-protective effects of dexamethasone may be partially realized by inhibiting the expression of NOS mRNA.

Applicability of various estimation formulas to assess renal function in Chinese children.

BACKGROUND: This study was to evaluate the relative applicability of the most commonly used estimation formulas for renal glomerular filtration rate (GFR) of Chinese children with chronic kidney disease (CKD). METHODS: One hundred CKD patients of less than 17 years old were divided into two groups by sex which was further categorized into five subgroups based on CKD staging according to the "reference" GFR (rGFR) determined by Tc-99m-DTPA renal dynamic imaging. Four GFR markers including serum cystatin C (CysC), ß2-microglobulin, creatinine, and blood urea nitrogen were measured. RESULTS: Among all four markers, CysC best reflected the extent of glomerular damages for CKD stage 1. The value for estimation of GFR (eGFR) was derived from five different formulas either over-estimated or underestimated GFR as referenced to rGFR, and the extent of deviations was dependent on gender, age and CKD stage. The Counahan-Barratt formula and the Schwartz formula gave the most accurate estimations of GFR for CKD stages 1 and 2-3, respectively regardless of gender and age differences. Receiver operating characteristic analyses indicated that the Counahan-Barratt formula has the highest diagnostic accuracy. CONCLUSION: The Counahan-Barratt formula provides the best approximation to rGFR, thereby the highest applicability to Chinese children with CKD of different genders, ages and CKD stages.

Therapeutic potential of EGCG on acute renal damage in a rat model of obstructive nephropathy.

As a major active component in green tea, (-)-epigallocatechin 3-O-gallate (EGCG) has many anti-oxidative activities. This study investigated whether intraperitoneal administration of EGCG was capable of suppressing oxidative stress in rats with unilateral ureteral obstruction (UUO) and probed the potential mechanisms involved. In total, 150 adult male rats were randomly divided into 5 groups (n=30 each): the control group (group N); the unilateral ureteral obstruction (UUO) group (group C), where the unilateral ureter was ligated resulting in an obstructive nephropathy model; and the EGCG group (group T), following unilateral ureteral ligation, rats were intraperitoneally injected with EGCG at a dosage of 2.5 (T1), 5 (T2) and 10 mg/kg/day (T3). Each group of rats was sacrificed 72 h after surgery. We evaluated the effects of EGCG on the reactive oxygen species (ROS), reduced glutathione (GSH), oxidized glutathione (GSSG) and glutathione in the renal tissue of rats. Immunohistochemistry and western blot analysis were applied to detect nuclear factor erythoid-derived 2-related factor 2 (Nrf2) and γ-glutamylcysteine synthetase (γ-GCS) protein expression. Real-time PCR was performed to detect the mRNA levels of Nrf2 and γ-GCS. Changes in renal ultrastructure were also observed using electron microscopy. There was no significant difference in GSH, and compared with group N, ROS, GSSG and total GSH levels were much higher in the T groups (p<0.01), while much lower than those of group C (p<0.01). Protein levels of Nrf2 and γ-GCS and the mRNA levels of Nrf2 and γ-GCS notably increased in EGCG-treated rats (all p<0.05). Furthermore, electron microscopy showed that renal ultrastructure was improved in the treatment groups. Our findings suggest that, resulting from suppression of oxidative stress influenced by free radicals, EGCG exerts a protective effect on rats with obstructive nephropathy, and this anti-oxidative effect may be partly induced by activating the Nrf2 signaling pathway.

[Changes of platelet endothelial cell adhesion molecule-1, tissue type plasminogen activator and plasminogen activator inhibitor-1 expression in the lung tissue of neonatal rats after intraperitoneal injection with lipopolysaccharide].

OBJECTIVE: To further explore the pathogenesis of neonatal acute lung injury and neonatal pulmonary hemorrhage by establishing the animal model of neonatal acute lung injury (ALI) and by investigating the changes of platelet endothelial cell adhesion molecule-1 (PECAM-1), tissue type plasminogen activator (t-PA) and plasminogen activator inhibitor-1 (PAI-1) in ALI. METHODS: Totally 88 neonatal rats which were divided into 8 groups randomly including one normal saline control group and 30 min, 1 h, 2 h, 4 h, 8 h, 16 h and 24 h post injection groups. The changes of lung pathology in newborn rats were observed at different time after LPS was injected intraperitoneally. The changes of PECAM-1 protein, t-PA and PAI-1 mRNA expression were measured by immunohistochemistry and RT-PCR. RESULTS: The expression of PECAM-1 protein and mRNA was decreased and the lowest level was reached at 8 h and 16 h post injection, respectively. The average values were 95.1 +/- 9.76 and 0.861 +/- 0.016, respectively, which were significantly lower than those in the control group (129.5 +/- 6.15, 1.192 +/- 0.035, P < 0.01). The expression of t-PA and PAI-1 mRNA was increased after LPS was injected. The highest level of t-PA mRNA expression was observed at 2 h after injection. The average value was 1.195 +/- 0.036, which was significantly higher than that in the control group (0.781 +/- 0.017, P < 0.01). The highest level of PAI-1 mRNA expression was observed at 2 h, 4 h and 8 h post injection. The average values were 1.178 +/- 0.069, 1.153 +/- 0.036 and 1.176 +/- 0.044, respectively, which was significantly higher than those of the control group (0.681 +/- 0.019, P < 0.01). CONCLUSIONS: The expression of PECAM-1 protein and mRNA was decreased after LPS injection, suggesting the disruption of the tissue protective mechanism; the expression of t-PA and PAI-1 mRNA was increased, indicating the presence of a hypercoagulability state. At the same time, the expression of t-PA mRNA was increased which caused the extra-cellular matrix degradation at the early phase after LPS injection. These three phenomena might be the contributory factors to pulmonary hemorrhage.

Evidence of increased DNA content of murine thymocytes caused by cocaine.

C57BL mice were injected intraperitoneally daily with 10 to 50 mg/kg of cocaine for five days. Four hours after the last injection, the thymuses were removed, and the effects on DNA and protein content of the surviving cells were measured. A dose-dependent increase in DNA content per cell, determined by UV spectrophotometric analysis, and a dose-dependent increase in protein content per cell, as measured using the Bio-Rad reagent, were observed. The increase in DNA content per cell was confirmed by H33258 staining of DNA as well as the diphenylamine assay. These changes were also observed when normal thymocytes were cultured with cocaine. Cell cycle analysis by flow cytometry of cocaine-treated cultures revealed the presence of aneuploid cells with increased DNA content. Fewer cells with aneuploidy were observed in experiments with significant apoptosis. Since both aneuploidy and enhanced apoptosis can be induced by cocaine and the amount of aneuploidy cells varies inversely with the degree of apoptosis, we hypothesize that cocaine causes DNA/chromosome damage, which eventually leads to cell death via the apoptosis pathway.