Risk Factors for Severe Hemorrhage Requiring Blood Transfusion Associated With Percutaneous Nephrolithotomy: A Systematic Review and Meta-Analysis

 

Abstract

Purpose: The aim of this meta-analysis was to systematically assess the risk factors for severe hemorrhage requiring blood transfusion associated with percutaneous nephrolithotomy, so that the urologist can prevent the occurrence of severe bleeding as soon as possible.

Materials and Methods: PubMed, Embase and The Cochrane Library were searched to collect the case-control studies on risk factors for severe hemorrhage requiring blood transfusion associated with percutaneous nephrolithotomy (PCNL) through Nov. 9, 2020. Eligible data was screened, extracted, and the risk of bias assessed independently by two qualified investigators. We then calculated the odds risks (ORs) and corresponding 95% confidence intervals (CIs) to assess the relationships between risk factors and severe hemorrhage requiring blood transfusion associated with PCNL.

Results: Eight case-control studies involving 5,974 patients were screened. In this meta-analysis, the risk factors were extracted as follow: gender, hypertension, diabetes mellitus, multiple tracts, staghorn calculi, previous PCNL, grade of hydronephrosis (moderate and severe), calyx of puncture (lower, middle, upper, multiple calices). Among them, diabetes mellitus (95% CI: 1.13 – 3.22, OR = 1.90, P = .016), multiple tracts (95% CI: 2.28 – 7.02, OR = 4.00, P = .000), staghorn calculi (95% CI: 1.34 - 4.08, OR = 2.34, P = .003), upper calyx (calyx of puncture) (95% CI: 0.40 - 0.86, OR = 0.59, P = .006), multiple calices (calyx of puncture) (95% CI: 1.79 - 3.20, OR = 2.39, P = .006) were statistically significant (all P < 0.05).

Conclusions: Our meta-analysis showed that diabetes mellitus, multiple tracts, staghorn calculi, multiple calices (calyx of puncture) are risk factors for severe hemorrhage requiring blood transfusion associated with PCNL, so we should focus on their prevention. Moreover, upper calyx (calyx of puncture) is a protective factor, the urologist may choose upper pole access as percutaneous nephrolithotomy tract to minimize intraoperative and postoperative blood loss

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Inhibition of Aortic Medial Calcification: miPEP-200b and miRNA-200b as Potential Mediators

Abstract

When considering the flow of genetic information in a cell, the traditional pathway of DNA to RNA to protein is what first comes to mind. In recent years, it has been clearly demonstrated that this pathway must be revised from new data and discoveries. The extensive study of noncoding RNA (ncRNA) has led to the discovery of many of its functions that were once unknown. Perhaps even more intriguing is our recent discovery that was made in an already new field of study. We demonstrated that primary microRNA-200a (pri-miRNA-200a) and pri-miRNA-200b possess open reading frames (ORF) that were recognized by ribosomes, allowing the pri-miRNAs to be translated into two peptides, miPEP-200a and miPEP-200b. Furthermore, studies have shown that these peptides are involved in the inhibition of cell migration in breast and prostate cancer cells and may even serve as significant prognostic markers of clinical outcomes. We have previously shown that miPEPs have downstream functional effects very similar to their miRNA counterparts, resembling many other protective mechanisms observed in nature. This “double-edged functional sword” allows for continued activity despite decreased functionality in one part of the system. Although the anti-neoplastic role of these peptides has recently been an area of interest, not much research has been published regarding their role in cardiovascular disease. In one study, it was demonstrated that a single nucleotide polymorphism in the gene coding for miRNA-200b might result in increased protein kinase A (PKA) activity that ultimately leads to activation of thrombocytes and ensuing atherosclerosis. PKA is not only involved in platelet activity but is rather known to play a role in a multitude of cellular pathways. Of interest is PKA’s involvement in medial aortic calcification, a process that has been implicated in isolated systolic hypertension (ISH); this condition is associated with increasing age. We hypothesize that in the same way that miRNA-200b plays a role in decreasing PKA activity in atherosclerotic processes, the peptide miPEP-200b may also act as an inhibitor of PKA-induced aortic medial calcification. If this association is shown to be present, focused therapy with miPEP-200b and miRNA-200b, along with PKA inhibitors, may significantly reduce the incidence, as well as prevalence, of isolated systolic hypertension in older age groups, leading to a decreased incidence of diastolic heart failure secondary to longstanding hypertension.

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Lupine Publishers | LOJ Pharmacology & Clinical Research

 Lupine Publishers | Profile of drugs used for prescription or not (selfmedication) by medical students

Introduction

According to the definition of the WHO Pharmaceutical Dictionary [1] and that of the European Directive 65/65, a medicinal product is “any substance or composition having curative or preventive properties with regard to human diseases. Indeed, any substance or composition that can be administered to humans for the purpose of establishing a medical diagnosis or restoring, correcting or modifying physiological functions in humans is also considered a medicinal product [1]. However, the irrational or non-rational use of drugs (poly pharmacy, inappropriate) is a major global problem, often in inadequate dosages. These common practices are also seen with students. Thus, for Adlaf et al, the prevalence of illegal psychotropic drug use (excluding cannabis in Canada) has been estimated at 52% [2]. For Koudou, students from UFR of Bouaké, consumed at least one drug during the examination period by self-medication [3]. Although medical students are expected to have habit of good practices and use of medicines, they face the same problems of access to medicines as the general population. Our objective was to study the profile of the drugs used as prescription and/or self-medication by medical students in order to identify the reasons, risks and adverse effects of their practices.

Materials and Methods

This cross-sectional study with descriptive aim took place from May 12 to June 14, 2019, including 234 medical students from the Preparatory School of Health Sciences (EPSS) at Nangui Abrogoua University and the UFR Medical Sciences of Abidjan (UFRSM). All medical students enrolled, regardless of gender, after informed consent were submitted. Students absent during the study period were excluded. The results were analyzed with Epi info 7 software.

Results and Comments

The average age of students was 21.28 ± 4.7 years, with age variation between 15 and 33 years (Figure 1); similar to Koudou’s study on the consumption of psychostimulants (20.6 ± 2.7 years) [3] and into that of Normand et al. on the intellectual doping of pharmacy students during the examination period (21 years) [5]. Thus, students were particularly young in health sciences. Our study showed male predominance (66.2%) with sex ratio of 1.9 comparable to another study in which surroundings school and university regardless the levels of study, this sex ratio varies from 2 to 4 [6]. Most of the students in our study were in Bachelor 2 (38.5%) or Master 1 (19.2%) but they were more students in L1 (first year license) at Koudou [3]. 38.5% of these students lived with their parents, 34.2% alone and 27.4% on university campuses. While according to Koudou [3] 48.1% of students lived with parents. This difference could be explained by the larger number of students in the group 600 compared to 234 in our study. Pathological reasons for using the drugs were headache, asthenia and fever respectively 31.3%, 8.7%and 16% (Table 1). The diagnoses mentioned were first malaria (37.6%), then influenza (17.1%) and typhoid fever (11.1%). These students were self-diagnosing as a result of the knowledge acquired during the lectures, and/or internships. Our results are superimposed with those of the work of Valentin et al [7] on the prevalence and characteristics of self-medication among students aged 18 to 35 residing at the Kasapa Campus of the University of Lubumbashi.

 

As for drugs (prescribed or taken as self-medication), the most used were antimalarials (58%), antibiotics (13%), analgesics and antipyretics (15.8%), but also some corticosteroids and antiulcers (Table 2). These same drugs were found in Konaté’s study on self-medication in pharmacies in the city of Sikasso (Mali) [8]. Thus, 70.5% of these students practiced self-medication and only 29.5% received prescriptions (Figure 2). Self-medication is a practice to be combated because self-diagnosis and treatment can be a source of error. This tendency to self-medication has been found in Valentin et al [7] among health science students. Indeed, 45.1% of them admitted to using self-medication and 54.9% of students of other sciences. The prescription could be legible in 71% of cases. The prescribed treatment was as outpatient in 79.7% of cases. The prescriber was a doctor in 56.5% or a PhD student in 26.1% of cases.

 

These observations described are intended to promote habits of good prescribing. Indeed, the prescription obeys rules that must be respected and known in order to comply with the recommendations. Students who practiced self-medication 65.5% had knowledge about side effects but 34.5% knew nothing about what constituted a danger. Almost all (97.4%) of the students did not perform paraclinical examinations to confirm the diagnosis either probably due to negligence or lack of financial means. For illustration, the average cost of treatment by self-medication was 2,962 fCFA with extremes of 200 and 25,000 fCFA. While that of the prescription was 10,323 fCFA with extremes of 400 and 61,000 fCFA (Table 3). The important thing is that self-medication was less expensive than drugs prescribed by a doctor. Some African studies [8, 9] have recognized that it is due to poverty, counterfeit medicines in the market [4], the proliferation of prescribers in our centers as well as the inaccessibility to doctors in our structures. Finally, the limitations of this work could be information biases. Indeed, some students refrained from answering questions when others were limited in understanding the questionnaire.

Conclusion

Medical students use few prescription drugs, and practice more self-medication because of the costs of treatment, hence the eternal problem of accessibility to care. It is time to put into circulation the health insurance card to help students treat themselves in order to reduce self-medication.

 

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Lupine Publishers | A Brief Review on Phytochemical and Pharmacological Aspects of Andrographis Paniculata

 Lupine Publishers | LOJ Pharmacology & Clinical Research

 

Introduction

Since the beginning of civilization, medicinal plants have been an intrinsic component of human life [1]. The conservation of ethnobotanical knowledge as part of living culture and practice between communities and the environment is essential for biodiversity conservation. The information about medicinal plants gains from various medicinal systems such as Unani, Siddha, and Ayurveda [2]. The traditional system of medicine belongs to the traditions of each country and has been passed over from generation to generation. Understanding the dynamics of traditional local knowledge of medicinal plants is important for their medicinal properties is now being developed as a source of scientific research to prove the effect of plants and generate new therapeutic resources. Medicinal plants are considered as a backbone of traditional medicine (WHO) as well as most modern medicine is also derived from medicinal plants i.e. aspirin. The medicinal plant having a rich source of components that can be used to develop and synthesize drugs. About 3.3 billion people in developing countries depend on medicinal plants on a regular basis, WHO estimated that about 80% world population rely on the medicinal plant for their primary health care. Further more, worldwide 42% of 25 top-selling drugs marketed are either directly obtained from natural sources or entities derived from plant products [3]. The quality of traditional medicine is determining its active substances produced by the plant. Andrographis paniculata is one of the important medicinal plants that is utilized throughout the world [4]. A.paniculata is an herbaceous plant of the Acanthaceae family. It is widely distributed in Southeast Asia, India, and tropical as well as in subtropical Asia. A.paniculata is also known as the “King of Bitters” since it has a highly bitter taste in all parts of the plant body [5]. Furthermore, A. paniculata is known as “Kalmegh” in India, “Chuan-Xin-Lian” in China, “Fah Tha Lai” in Thailand, “Hempedu Bumi” in Malaysia, “Senshinren” in Japan, and “green chiretta” in Scandinavian nations [6]. A.paniculata is one of the most widely used plants in Ayurvedic and Unani medicine [4]. Traditionally, A.paniculata was used in the treatment for snakebite, fever, bug bite, diabetes, malaria, and dysentery [7]. Moreover, A.paniculata is also used in the combination with other herbs and health care treatment. It is found that A.paniculata is used in more than half of the herbal formulations commercialized in India for he patic diseases [8]. Many scientific studies also have been reported regarding the medicinal properties possessed by the A.paniculata, most of which are based on traditional knowledge (Table 1). Phytochemical investigations have revealed that A. paniculata contains a wide range of chemicals. In addition, experimental evidence also reported that A.paniculata has a broad spectrum of pharmacological activity including anti-bacterial, antidiarrheal, anti-inflammatory, antiviral, antimalarial, anticancer, antimalarial, hepatoprotective, etc. In this review, we briefly discuss ethnobotanical uses, phytochemistry, and recent scientific finding pharmacological activity of the A.paniculata [6].

Table 1: Taxonomical classification of Androgrphis paniculata.

Botanical Description and Habitat

A.paniculata is native species of India, China, and Taiwan. But it is also found in Southeast Asia, tropical and subtropical Asia as well as few other nations such as Malaysia, Indonesia, Vietnam, Sri Lanka, Laos, Cambodia, Pakistan, Myanmar, and the Caribbean islands [9]. Especially, in India A.paniculata are found in Karnataka, Andhra Pradesh, Tamil nadu, Uttar Pradesh, and Madhya Pradesh. Also cultivated in Assam and West Bengal to some extent. In addition, A.paniculata are found in different habitats including forests, farms, plains, hill slopes, dry and wetlands, and wastelands [10]. A.paniculata is bitter in test, an annual herb that is abundantly branched which grows up to a height of 3.-110 cm in a humid, shady area. It has glabrous leaves that are 8.0 cm long and 2.6 cm wide, little white flowers that are rose-purple or light pink, spots on the petals, and corolla with hairs. The stem was found to be dark green in color, 0.4-1.0 m tall, 2-6 mm in diameter, quadrangular with longitudinal furrows and wings on the angles of the younger part [11] as shown in Figure 1.

Figure 1: Andrographis paniculata morphology.

Traditional Uses of Andrographis Paniculata

A.paniculata play vital importance in the Ayurvedic, Siddha, and traditional medicine systems in India [12]. For centuries, the leaves and roots of A.paniculata have been used to treat a wide range of health problems in Asia and Europe. However, the entire plant is also utilized for specific uses [13]. The plant known as “Kalmegh” in Ayurvedic literature is an essential element in the majority of Ayurvedic remedies and is officially recognized by Ayurvedic pharmacopeia. Moreover, it is used as an aperient, emollient, astringent, anti-inflammatory, diuretic, anthelmintic, carminative, and antipyretic in the Unani system of medicine [14].In India, tribal groups used this herb to cure a number of diseases such as antidote against snake bites, Banded Krait and Russell’s viper, etc. [14]. The tribal of Kheria, Khatra, Moora, and the Santal region of Bankura district, West Bengal, India utilizes an infusion of the entire plant to treat fever [15]. The extracted juice from A.paniculata leaves, alone or combined with cloves, cinnamon, and cardamom is used as a cure for flatulence, loss of appetite, griping, diarrhea in children, and irregular stool. In India during the influenza epidemic in 1919, A.paniculata was shown to be highly effective in reducing the disease progression [16]. It was also utilized by ancient Chine’s physicians to treat inflammatory diseases, colds, laryngitis, and fever, hepatitis, pneumonia, respiratory infections, tonsillitis, sores, pelvic snake bites, herpes zoster and it has been characterized as a cold property herb [13] to remove toxins and body heat. The decoction of fresh leaves of A.paniculata is used as an antihypertensive and antidiabetic in Malaysian folk medicine. Furthermore, it is advised to use it in cases of leprosy, scabies, gonorrhea, boils, chronic and seasonal fevers, and skin eruptions, due to its “blood purifying” purifying properties [4].

Phytochemistry

The aerial part (leaves and stems) of A. paniculata contains major active phytochemicals [17]. According to the survey of the literature, andrographolide is the major bioactive compound found in the A.paniculata which is a diterpene lactone that is crystalline, colorless, and has a bitter taste [9]. The leaves have the highest concentration of andrographolide about 2.39% whereas the seed has the lowest concentration about 0.58%. The quantity of the phytochemicals varies widely depending on the portion used, locality, time of harvesting, and season (Figure 2). Andrographolides are highest found immediately before the flowering season, then decline progressively [14]. Other lactones compound observed in A.paniculata is 14-deoxy-11-andrographolide, 14-deoxy-11, 12 didehydroandrographolide, andragraphan, andrographon, 14-deoxyandrographolide, neoandrographolide, deoxyandrographiside, andrographosterol, andrographiside etc. A.paniculata also contains Xanthones and quinic acid derivatives in minor concentrations. Moreover, Reddy et a. [18] reported that A.paniculata contains flavone such as 5-hydroxy-7’2’6’-trimethoxyflavone and 23-C terpenoid 14-deoxy-15-isopropylidene-11, 12- didehydroandrograholide and other flavonoid Skullcapflavone I 2’-O-glucoside, 7-Omethylwogonin, 7-Omethyldihydrowogonin and 7-O-methylwogonin 5-O-glucoside as well as diterpenoids such as isoandrographolide 14-deoxy-11, 12 didehydroandrographolide. Rao et al. [19] identified and isolated 5, 7, 20, 30-tetramethoxyflavanone and 5-hydroxy-7, 20, 30-trimethoxy flavone from the A.paniculata. A new labdane type diterpenoid which is andropanolide along with seven known diterpenoids isolated from the methanolic leaves extract of A.paniculata [20].

Figure 2: Chemical structure of major component found in A.paniculata.

Pharmacological Activity of A.Paniculata

Hepatoprotective activity

A.paniculata is widely used as a hepatoprotective and hepatostimulative agent in the Indian traditional medicine system. Traditionally the leaves aqueous extract of A.paniculata is used in the treatment of jaundice and different liver damage. Andrographolide found in the A.paniculata was protective against liver damage in rats and mice induced by carbon tetrachloride. Moreover, Andrographolide also observed significant hepatoprotective against various types of liver damage, induced by galactosamine or paracetamol [21]. The free radical scavenging activity of andrographolide has a significant hepatoprotective effect by lowering lipid peroxidation malondialdehyde product as well as by maintaining glutamic pyruvate transaminase, alkaline phosphatase, and glutathione levels in mice treated with carbon tetrachloride [22]. A.paniculata has been shown antihepatotoxic activity against plasmodium berghei K173-induced hepatic damage in mastomys natalensis [23].

Antibacterial activity

A.paniculata has been shown the antibacterial activity against a wide range of bacterial species. In vitro study found that the aqueous extract of A.paniculata shown antibacterial activity even at the low concentration (25 mg/ml) against E.coli, Shigella, Streptococci, Staphylococcus aureus, and Salmonella [24]. Another similar study leaves aqueous extract of A.paniculata reported against the methicillin- resistant S.aureus and Pseudomonas aeruginosa [25]. Furthermore, A.paniculata is also effective against HAS 1 (herpes simplex virus 1) without any cytotoxicity [26].

Antidiarrheal activity

In developing countries, Diarrhea is one of the most common diseases and it leads to the top ten causes of death among children worldwide [5]. Some drugs such as kaolin-pectin, selenium, loperamide, and bismuth have been used to treat the symptoms. However, it also causes some unfavorable side effects [5]. The study has been found that A.paniculata has significant antidiarrheal properties [27]. According to the study, an ethanolic extract of A.paniculata treated 88.3 % of acute bacillary dysentery cases and 91.3% of acute gastroenteritis cases. Furthermore, andrographolide was found to treat 91% of acute bacillary dysentery cases. The same cure rate of about 91.1% was obtained by providing a compound tablet comprising andrographolide and neoandrographolide in a 7:3 ratio. This was claimed to be more than the cure rate observed with chloramphenicol and furazolidone [28]. A.paniculata was found to be effective in curing patients with acute diarrhea and bacillary dysentery in double-blind investigation [14].

Antimalarial activity

In many tropic and subtopic countries, malaria is still a prevalent disease [14]. A.paniculata was shown to significantly suppress the growth of the Plasmodium berghei [11]. In vitro study of 50% ethanolic extract of the aerial parts (100 mg/g) shown antimalarial activity against plasmodium berghei and in vivo study in rats observed antimalarial activity after intragastric application (1g/kg body weight) [26]. It is suggested that the antimalarial effect of A. paniculata is due to the reactivation of the enzyme superoxide dismutase [5]. Another study has been reported that the crude extract of A.paniculata shown antimalarial activity against the resistant strain of Plasmodium falciparum having an IC50 value of 6mg/ml [29]. In addition, a xanthous compound isolated from the A. paniculata has been shown in vivo antimalarial activity in plasmodium infected Swiss albino mice. The results found that a significant reduction in parasitemia after treatment with a 30 mg/kg dosage [26].

Anticancer activity

Cancer is a set of disorders characterized by abnormal cell proliferation and the ability to penetrate or be spared to other regions of the body. Despite the fact that many diseases have a worse prognosis than most cancers [17]. The extract of A.paniculata having diterpenoid is significantly able to restrict cell proliferation, arrest the cell cycle and induce cell apoptosis of different cancer cells [30- 33]. Treatment of the MDA-MB-231 breast cancer cells with andrographolide extracted from A. Paniculata causes apoptosis of cancer cells and arrests the cell cycle without interfering with the normal growth of cells [34]. The study has been reported that A.paniculata exhibits potent cytotoxic activity against human epidermoid carcinoma of the skin lining of the lymphocytic leukemia cells and nasopharynx [12]. A.paniculata also shown cytotoxic effects against colon cancer cells by suppressing AKT and mTOR phosphorylation levels, resulting in ER stress-induced death [35]. Furthermore, apoptosis in colon cancer cells is induced by the andrographolide via controlling the signaling of pro-apoptotic GRP-78/IRE1/XBP-1/ CHOP [17].

Antidiabetic activity

Diabetes is a metabolic disease characterized by elevated blood sugar levels [36]. According to the WHO reports around 70 million people worldwide suffer from diabetes. Specifically in developing countries, diabetes has become a threat to human health [37]. In vivo study observed that ethanolic extract of A.paniculata exhibit the protective effect in hyperglycemic condition and also protect the tissue damage caused due to oxidative stress in a diabetic rat model produced by streptozotocin [38]. Another study conducted [39] found that oral administration of andrographolide in a dose-dependent manner reduced plasma glucose levels in diabetic rats caused by streptozotocin and wild-type rats.

Conclusion

The entire literature review indicated that Andrographis paniculata exhibits a broad range of phytochemicals and pharmacological activities. The previous study found that A.paniculata contains 50 lactane diterpenoids, 30 flavonoids, and 30 novels phytochemical isolated and identified from A.paniculata. Phytochemical study reveals that Andrographolide is a major compound found in Andrographis paniculata. It has shown a wide spectrum of pharmaceutical activity such as anti-microbial, hepatoprotective activity, anti-inflammatory activity, anti-malarial, anti-diarrheal, anti-diabetic, and cytotoxic activity. The precise information offered as a review here covers the phytochemical and pharmacological information about this plant, providing the muchneeded encouragement to use this plant in creating and sustaining a prospective means of livelihood.

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