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Fulltext Flaccid paralysis in an infant associated with a dirty wound and application of honey

Joseph CJ, Khoo TB, Lee KY

BMJ Case Rep, 2017 Jan 06;2017.
PMID: 28062435 DOI: 10.1136/bcr-2016-218044

An infant, who was born preterm at 36 weeks, presented with fever and ulcer at umbilical region which progressed to necrotising fasciitis of anterior abdominal wall. He was treated with intravenous penicillin, intravenous cloxacillin and local application of medicated honey. Subsequently, he required wound debridement. Postoperatively, he required prolonged invasive ventilation due to poor respiratory effort which was associated with hypotonia and areflexia. Nerve conduction study revealed absent responses. The diagnosis of infant botulism was made based on the clinical presentation, nerve conduction study and his clinical progress. Botulinum immunoglobulin was not available. He was treated with intravenous immunoglobulin and oral pyridostigmine. He was successfully extubated after 37 days, and currently the patient is doing well.

Matched MeSH terms: Cholinesterase Inhibitors/therapeutic use*
Lactobacilli-fermented cow's milk attenuated lipopolysaccharide-induced neuroinflammation and memory impairment in vitro and in vivo

Musa NH, Mani V, Lim SM, Vidyadaran S, Abdul Majeed AB, Ramasamy K

J Dairy Res, 2017 Nov;84(4):488-495.
PMID: 29154736 DOI: 10.1017/S0022029917000620

Nutritional interventions are now recommended as strategies to delay Alzheimer's disease (AD) progression. The present study evaluated the neuroprotective effect (anti-inflammation) of lactic acid bacteria (either Lactobacillus fermentum LAB9 or L. casei LABPC) fermented cow's milk (CM) against lipopolysaccharide (LPS)-activated microglial BV2 cells in vitro. The ability of CM-LAB in attenuating memory deficit in LPS-induced mice was also investigated. ICR mice were orally administered with CM-LAB for 28 d before induction of neuroinflammation by LPS. Learning and memory behaviour were assessed using the Morris Water Maze Test. Brain tissues were homogenised for measurement of acetylcholinesterase (AChE), antioxidative, lipid peroxidation (malondialdehyde (MDA)) and nitrosative stress (NO) parameters. Serum was collected for cytokine analysis. CM-LAB9 and CM-LABPC significantly (P < 0·05) decreased NO level but did not affect CD40 expression in vitro. CM-LAB attenuated LPS-induced memory deficit in mice. This was accompanied by significant (P < 0·05) increment of antioxidants (SOD, GSH, GPx) and reduction of MDA, AChE and also pro-inflammatory cytokines. Unfermented cow's milk (UCM) yielded greater cytokine lowering effect than CM-LAB. The present findings suggest that attenuation of LPS-induced neuroinflamation and memory deficit by CM-LAB could be mediated via anti-inflammation through inhibition of AChE and antioxidative activities.

Matched MeSH terms: Cholinesterase Inhibitors/administration & dosage
Myasthenia gravis and a rare complication of chemotherapy

Ng CV

Med J Aust, 2005 Feb 07;182(3):120.
PMID: 15698357

We describe a patient with myasthenia gravis and thymoma who developed recurrent severe myasthenic crises associated with the use of combination chemotherapy.

Matched MeSH terms: Cholinesterase Inhibitors/administration & dosage
Fulltext "Why do I always see double?" A misdiagnosed case of ocular myasthenia gravis for 10 years

Yousuf UA, Yashodhara BM, Thanigasalam T, Ting HS

BMJ Case Rep, 2014 May 02;2014.
PMID: 24792021 DOI: 10.1136/bcr-2013-203488

A 58-year-old man presented with diplopia and partial ptosis for 10 years. It was non-progressive in nature, despite inadequate medical attention the patient received from non-specialists/general practitioners. He did not have fatigability or diurnal variation in weakness and was clinically stable without exacerbations of disease for a decade. He did not have features of Graves's disease, oculopharyngeal dystrophy, cranial nerve paralysis, polymyositis and stroke. The possibility of an atypical presentation of myasthenia gravis (MG) was considered and the patient was evaluated. Ice pack test was negative, Cogan's lid twitch (CLT) test was positive and high titres of acetylcholine receptor antibodies (AChR Ab) suggestive of MG were found. He was treated accordingly with a very good response.

Matched MeSH terms: Cholinesterase Inhibitors/therapeutic use
Fulltext Phytochemicals content, antioxidant activity and acetylcholinesterase inhibition properties of indigenous Garcinia parvifolia fruit

Ali Hassan SH, Fry JR, Abu Bakar MF

Biomed Res Int, 2013;2013:138950.
PMID: 24288662 DOI: 10.1155/2013/138950

Garcinia parvifolia belongs to the same family as mangosteen (Garcinia mangostana), which is known locally in Sabah as "asam kandis" or cherry mangosteen. The present study was conducted to determine the phytochemicals content (total phenolic, flavonoid, anthocyanin, and carotenoid content) and antioxidant and acetylcholinesterase inhibition activity of the flesh and peel of G. parvifolia. All samples were freeze-dried and extracted using 80% methanol and distilled water. For the 80% methanol extract, the flesh of G. parvifolia displayed higher phenolic and flavonoid contents than the peel, with values of 7.2 ± 0.3 mg gallic acid equivalent (GAE)/g and 5.9 ± 0.1 mg rutin equivalent (RU)/g, respectively. Anthocyanins were detected in the peel part of G. parvifolia but absent in the flesh. The peel of G. parvifolia displayed higher total carotenoid content as compared to the flesh part with the values of 17.0 ± 0.3 and 3.0 ± 0.0 mg β-carotene equivalents (BC)/100 g, respectively. The free-radical scavenging, ferric reducing, and acetylcholinesterase inhibition effect of the flesh were higher as compared to the peel in both extracts. These findings suggested that the edible part of G. parvifolia fruit has a potential as a natural source of antioxidant and anti-Alzheimer's agents.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology*
Jatropha gossypiifolia L. and its biologically active metabolites: A mini review

Wu Q, Patocka J, Nepovimova E, Kuca K

J Ethnopharmacol, 2019 Apr 24;234:197-203.
PMID: 30695706 DOI: 10.1016/j.jep.2019.01.022

ETHNOPHARMACOLOGICAL RELEVANCE: Jatropha gossypiifolia L. (Euphorbiaceae) is popularly known as bellyache bush or black physic nut and is widely used in local / traditional medicine due to the various biological activities attributed to its different parts, including its leaves, roots, and latex.
AIM OF THE STUDY: In this review, we aim to update and discuss the chemistry, specific pharmacology, and toxicological activities of Jatropha gossypiifolia and its bioactive metabolites.
MATERIALS AND METHODS: The Web of Science, PubMed, Google Scholar, SciFinder, Cochrane Library, Scopus, and Science Direct databases were searched with the name "Jatropha gossypiifolia" and the term "bioactive metabolites". All studies on the chemistry, pharmacology, and toxicology of the plant up to December 2018 were included in this review.
RESULTS: Jatropha gossypiifolia leaves are considered to have anti-inflammatory, antimicrobial and insecticidal properties. The root and stem have anti-inflammatory and antimicrobial properties. The seeds and fruits can be used against influenza and as a sedative, analgesic or anti-diarrheal agents. The latex is bactericidal and molluscicidal. Topical application of latex is used to treat wounds and bites of venomous animals. The diluted form is usually used for the treatment of diarrhoea by indigenous peoples.
CONCLUSIONS: The main pharmacological activities of Jatropha gossypiifolia include anti-inflammatory, antineoplastic, antimicrobial, antioxidant, and anticholinesterase, and antihypertensive activities. Species of Jatropha are notably known for their toxic potential, and their toxicity is primarily related to the latex and seed contents. However, the potential mechanisms of these pharmacological activities have not been fully explored. We hope this review will help to further inform the potential utilization of Jatropha gossypiifolia in complementary and alternative medicine.

Matched MeSH terms: Cholinesterase Inhibitors
A molecular approach in drug development for Alzheimer's disease

Agatonovic-Kustrin S, Kettle C, Morton DW

Biomed Pharmacother, 2018 Oct;106:553-565.
PMID: 29990843 DOI: 10.1016/j.biopha.2018.06.147

An increase in dementia numbers and global trends in population aging across the world prompts the need for new medications to treat the complex biological dysfunctions, such as neurodegeneration associated with dementia. Alzheimer's disease (AD) is the most common form of dementia. Cholinergic signaling, which is important in cognition, is slowly lost in AD, so the first line therapy is to treat symptoms with acetylcholinesterase inhibitors to increase levels of acetylcholine. Out of five available FDA-approved AD medications, donepezil, galantamine and rivastigmine are cholinesterase inhibitors while memantine, a N-methyl d-aspartate (NMDA) receptor antagonist, blocks the effects of high glutamate levels. The fifth medication consists of a combination of donepezil and memantine. Although these medications can reduce and temporarily slow down the symptoms of AD, they cannot stop the damage to the brain from progressing. For a superior therapeutic effect, multi-target drugs are required. Thus, a Multi-Target-Directed Ligand (MTDL) strategy has received more attention by scientists who are attempting to develop hybrid molecules that simultaneously modulate multiple biological targets. This review highlights recent examples of the MTDL approach and fragment based strategy in the rational design of new potential AD medications.

Matched MeSH terms: Cholinesterase Inhibitors/metabolism; Cholinesterase Inhibitors/pharmacology*; Cholinesterase Inhibitors/chemistry
Fulltext Recent updates in the treatment of neurodegenerative disorders using natural compounds

Rasool M, Malik A, Qureshi MS, Manan A, Pushparaj PN, Asif M, et al.

Evid Based Complement Alternat Med, 2014;2014:979730.
PMID: 24864161 DOI: 10.1155/2014/979730

Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer's disease, Parkinson's disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

Matched MeSH terms: Cholinesterase Inhibitors
Fulltext In-vitro and in-vivo validation of ethnopharmacological uses of methanol extract of Isodon rugosus Wall. ex Benth. (Lamiaceae)

Janbaz KH, Arif J, Saqib F, Imran I, Ashraf M, Zia-Ul-Haq M, et al.

BMC Complement Altern Med, 2014 Feb 22;14:71.
PMID: 24559094 DOI: 10.1186/1472-6882-14-71

BACKGROUND: Isodon rugosus is used in folk Pakistan traditional practices to cure ailments related to gastrointestinal, respiratory and cardiovascular problems. Present study was undertaken to validate these folkloric uses.
METHODS: A crude methanol extract of the aerial parts of Isodon rugosus (Ir.Cr.) was used for both in vitro and in vivo experiments. The plant extract was tested on isolated rabbit jejunum preparations for possible presence of spasmolytic activity. Moreover, isolated rabbit tracheal and aorta preparations were used to ascertain the relaxant effects of the extract. Acetylcholinesterase and butyrylcholinesterase inhibitory activities of Ir.Cr were also determined as well as its antioxidant activity. The in vivo antiemetic activity of the extract was evaluated by using the chick emesis model, while the analgesic and antipyretic activities were conducted on albino mice.
RESULTS: The application of the crude extract of I. rugosus to isolated rabbit jejunum preparations exhibited relaxant effect (0.01-0.3 mg/ml). The Ir.Cr also relaxed K+(80 m M)-induced spastic contractions in isolated rabbit jejunum preparations and shifted the Ca+2 concentration response curves towards right (0.01-0.3 mg/ml). Similarly, the extract, when applied to the isolated rabbit tracheal preparations relaxed the carbachol (1 μM)--as well as K+ (80 mM)-induced contractions in a concentration range of 0.01-1.0 mg/ml. Moreover, it also relaxed (0.01-3.0 mg/ml) the phenylephrine (1 μM)- and K+ (80 mM)-induced contractions in isolated rabbit aorta preparations. The Ir.Cr (80 mg/kg) demonstrated antipyretic activity on pyrogen-induced pyrexia in rabbits as compared to aspirin as standard drug. The Ir.Cr also exhibited anti-oxidant as well as inhibitory effect on acetyl- and butyryl-cholinesterase and lipoxygenase (0.5 mg/ml).
CONCLUSIONS: The observed relaxant effect on isolated rabbit jejunum, trachea and aorta preparations caused by Ir.Cr is possibly to be mediated through Ca+2 channel blockade and therefore may provided scientific basis to validate the folkloric uses of the plant in the management of gastrointestinal, respiratory and cardiovascular ailments. The observed antioxidant activity as well as the lipoxygenase inhibitory activity may validate its traditional use in pain and inflammations.

Matched MeSH terms: Cholinesterase Inhibitors/pharmacology; Cholinesterase Inhibitors/therapeutic use
Anti-acetylcholinesterase, anti-α-glucosidase, anti-leishmanial and anti-fungal activities of chemical constituents of Beilschmiedia species

Mollataghi A, Coudiere E, Hadi AH, Mukhtar MR, Awang K, Litaudon M, et al.

Fitoterapia, 2012 Mar;83(2):298-302.
PMID: 22119096 DOI: 10.1016/j.fitote.2011.11.009

Phytochemical investigation of Beilschmiedia alloiophylla has resulted in the isolation of one new alkaloid, 2-hydroxy-9-methoxyaporphine (1), and ten known natural products, laurotetanine (2), liriodenine (3), boldine (4), secoboldine (5), isoboldine (6), asimilobine (7), oreobeiline (8), 6-epioreobeiline (9), β-amyrone (10), and (S)-3-methoxynordomesticine (11). Chemical studies on the bark of B. kunstleri afforded compounds 2 and 4 along with one bisbenzylisoquinoline alkaloid, N-dimethylphyllocryptine (12). Structures of compounds 1-12 were elucidated on the basis of spectroscopic methods. All of these isolates were evaluated for their anti-acetylcholinesterase (AChE), anti-α-glucosidase, anti-leishmanial and anti-fungal activities. Compounds 1-12 exhibited strong to moderate bioactivities in aforementioned bioassays.

Matched MeSH terms: Cholinesterase Inhibitors