Poppy Capsules Research Articles

Review on Toxicological Aspect of Ahiphena (Papaver)

Ahiphena (papaver) is one among Upavisha which is air-dried latex juice obtained from unripe capsules of white poppy. White poppy is botanically classified as Papaver somniferum and belongs to family Papaveracea The name poppy is derived from Latin meaning sleep inducing. The Ayurvedic text Rasa Tarangini Included Ahiphena (papaver) among eleven Upavishas . Opium yields wide range of natural, semi synthetic and synthetic alkaloids namely morphine, thebaine, codeine and papaverine which is commonly use in medicine. Semi synthetic heroin, hydro morphine, oxymorphone, oxycodone and synthetic meperidine, methadone, levarphanol , diphenoxylate, fentanyl, proposophene. Opium and its alkaloids cause drug dependence and it is most commonly abused substances after cannabis. Opioids are the main drugs of abuse in Asia, Europe and much of Oceania. The opium act of 1857 empowers only Central Government to cultivate poppy plants and manufacture opium with the help of farmers authorized by Government. The opium act 1878 prohibits import, export, transportation, possession and sale of opium. The Narcotic Drugs and Psychotropic Substances Act, 1985 includes opium as narcotic and psychotropic substances and consumption of opium and its leads to imprisonment for one year or with fine or with both. Schedule-E (1) of Drugs & Cosmetics Act, 1940 has included opium in list of poisons. This study design to present all toxicological aspect of Ahiphena in Ayurvedic and contemporary View to treat people of opium poisoning and counselling in drug abuse.

SOMNIFERA

“Somnifera” explores interactions between the opium poppy and humans. In their exploration of new habitats, human tribes curiously tested out plants that could help them transcend their “normal” state into expanded experiences, possibly communicating with their ancestors or gods, as part of their experimental quest for knowledge. Since the dawn of time, we have milked the benefits of the opium plant, while politics, religion, and a cynical multinational drug and pharmaceutical industry have assigned the plant a controversial role on the world stage. The plant’s power to both save life and take life is the essence of this artwork with the intention to contribute to a holistic debate about the opium poppy’s potential: To lift it out of the shadow of condemnation and give it its rightful bright place among us. This narrative dips in and out between trance-states and every-day-states-of-mind, while the author’s alter ego Sigma Woman enters love and grief – transitioning from emotional breakdown to possible healing. The figurative language of this text, and its accompanying images, are from visions emerging from ecstatic trance – described as the primaeval technique of a safe, natural physiological transition to direct experience of the eternal now and ancestral wisdom. In one of the trance-sessions we concentrated on the three-thousand-year-old figurine “The Poppy Goddess and Patron of Healing.” This inner journey gave rise to the idea of exploring reenactment, inspired by experimental archaeology. Approaching the goddess figure, the author anoints her body with Caput Mortuum-colored oxidized magnetite, adorns herself with poppy capsules, and mimics the statue’s apparent hibernation. In the attempts to find “surfaces of contact” between today’s imaginary world and prehistoric times – through speculation whether we and our ancestors can “meet” in some way – the methods used to develop the artwork range from knowledge acquisition through scientific papers to techniques for embodying knowledge. As part of the artistic research project Matter, Gesture and Soul (MGS), which seeks encounters and alignments between art and archaeology, my artistic contribution seeks to question how multispecies storytelling may connect us emotionally to our ancient distant past.

Determination of the Field Performance of a Prototype Combined Poppy Harvester

HighlightsA poppy harvester can be used as an alternative to the manual harvesting.Effective field capacity of a poppy harvester is 34 to 53 times higher than the manual harvest.Depending on the forward speed, field losses increase.Cleaning efficiency can be increased by a more aggressive sieving application.Abstract. The operations of collecting the poppy from the field by hand and then breaking it apart require intensive labor and time consumption, which increases the cost significantly. A mechanical harvester to be used for poppy harvesting will save human labor and reduce time consumption. Hence, a poppy harvester was designed to harvest and crush poppy capsules, and separate the stalks, seeds, and capsule parts from the shredded material with this study. The prototype harvester consists of a harvest unit, conveying unit, threshing unit, separating and cleaning unit, bagging unit, and power transmission unit. The machine is pulled by the tractor and its moving units are driven by the PTO and hydraulic system. In field experiments with the prototype poppy harvester, the material capacity of the machine (seed, capsule pieces, and total product), cleaning efficiency, and harvest losses were determined. The experiments were conducted in a randomized complete block design with three replicates. The prototype machine was operated at two forward speeds of 1.24 km h-1 and 1.95 km h-1. The effective field capacity of the harvester was determined to be 34 to 53 times higher than the manual harvest, and increasing forward speed, increased machine capacity by approximately 50%. The cleaning efficiency was determined to be approximately 84% for both forward speeds. Depending on the forward speed, field losses increased and varied between 13% and 21%. Keywords: Keywords., Cleaning capacity, Field losses, Harvesting capacity, Poppy harvester.

Voyage of Ben Cao, Part II: Development of Chinese Medicinal Specimens in the British Museum

Voyage of Ben Cao, Part II: Development of Chinese Medicinal Specimens in the British Museum

Forensic Application of Genetic and Toxicological Analyses for the Identification and Characterization of the Opium Poppy (Papaver somniferum L.).

Simple SummaryThe identification and characterization of illicit plant species such as Papaver somniferum L. (opium poppy) are essential in order for law enforcement agencies to obtain information about the origin of seized drugs, and to improve the monitoring of illegal drug trafficking routes. This study focuses on the genetic and toxicological analyses of some poppy capsules seized by the Italian Police Forces in 2017 and 2018. The detection of specific morphological traits, the chemical study of the alkaloid profile by gas chromatography coupled with mass spectrometry (GC/MS), and the genetic analysis performed by the DNA barcode approach showed that the seized poppy capsules belonged to P. somniferum. The data collected also suggested that the opium capsules originated from Afghanistan.Background: A reliable and science-based taxonomic determination of Papaver somniferum L. (opium poppy), the illegal species of the genus Papaver, may have practical and legal implications for law enforcement. P. somniferum is a controlled plant because of its narcotic substances, such as morphine and codeine. As poppy plants have rather similar morphological features, both chemical and genetic analysis are required in order to achieve an accurate characterization of such species. The chemical structures of alkaloids are extremely variable even within the same species, which is why the genetic approach may lead to a more scientific Papaver sp. differentiation. The aim of our study was the taxonomic identification of poppy capsules seized by the Italian Police Forces being considered as potential P. somniferum derivatives. Methods: The alkaloids detected using gas chromatography/mass-spectrometry (GC/MS) were morphine, codeine, thebaine, noscapine, meconin, hydrocotarnine, and traces of papaverine. Further genetic analysis was carried out simultaneously using three plastid DNA barcoding regions (matK, trnH-psbA, and rbcL) for the samples’ identification. Results: The Random Amplification of Polymorphic DNA (RAPD) method showed that the analysed samples were genetically identical. Conclusions: The morphological, toxicological, and genetic profile of the samples revealed that they belonged to P. somniferum species. Furthermore, the alkaloid content of dried poppy capsules might be used to investigate and track their origin.

Spatial Distribution and Stability of Cholinesterase Inhibitory Protoberberine Alkaloids from Papaver setiferum.

During a research program to identify new cholinesterase inhibitors of natural origin, two new 7,8-didehydroprotoberberine alkaloids (1 and 2) and nine known compounds (3–11) were isolated from the capsules of the common ornamental poppy, Papaver setiferum (previously P. pseudo-orientale). Despite their reported instability, the 7,8-didehydroprotoberberines isolated herein appeared relatively stable, particularly as their trifluoroacetic acid salts. The spatial distributions of the isolated alkaloids were also analyzed using desorption electrospray ionization imaging mass spectrometry. The alkaloids were localized predominantly within the walls and vascular bundles of the capsules, with the highest relative abundances occurring in the lower half of the capsules toward the peduncle. The relative abundances of the alkaloids were also compared across plant development stages. Although most alkaloids did not show clear patterns in their concentration across development stages, the concentration of suspected oxidation products clearly spiked upon plant death. Finally, all isolated natural products were screened for inhibitory activities against a panel of cholinesterases, from both human and animal sources. These studies identified several competitive inhibitors of cholinesterases with potency in the low micromolar range (1–4, 6, 7), offering new lead compounds for the development of cholinesterase inhibitory drugs.

Rapid determination of twelve bioactive components in rat plasma by UHPLC-MS/MS and its application to pharmacokinetic and in vitro-in vivo correlation study of compound liquorice tablets

Compound liquorice tablets (CLQTs), composed of Licorice Extract (LE), Powered Poppy Capsule Extractive (PPCE), Camphor, Oleum Anisi Stellati and sodium benzoate, is widely used for antitussive and expectorant. A fast, selective and sensitive UHPLC-MS/MS method for determination of seven flavonoids (liquiritin, isoliquiritin, neoisoliquiritin, liquiritigenin, isoliquiritigenin, liquiritin apioside, and isoliquiritin apioside), two triterpene saponins (glycyrrhizic acid and glycyrrhetinic acid), two isoquinoline alkaloid (codeine and morphine), one aromatic (trans-anethole) in rat plasma was developed and validated. Then, the proposed method was used to investigate the pharmacokinetic differences of eleven bioactive components in rats after administration of CLQTs and the single herb (LE or PPCE). The results showed that LE acted synergistically with PPCE by prolonging the efficacy of CLQTs. Subsequently, based on an AUC-weighting approach, the integrated pharmacokinetics of twelve bioactive components was determined, which might provide a more comprehensive understanding of the relationship between the pharmacokinetic behaviors of herbal medicine. Additionally, in view of the synthetic effect of complex chemicals in traditional Chinese medicine, we put forward a flow-injection analysis method to determine the total components dissolution profile of CLQTs. Finally, the integral pharmacokinetic parameter (lnC) and the cumulative dissolution (Pmr(i)) were used to explore the in vitro-in vivo correlations preliminarily and the R2 was above 0.9383. This study provided more insight for further understanding of the compatibility mechanism of CLQTs and improved the safety and rationality of the clinical use of CLQTs.

Quality monitoring and evaluation of Powdered Poppy Capsule Extractive by multiple wavelengths matching average fusion chromatographic fingerprint combined with electrochemical fingerprint

As quality determined the effectiveness and safety of the drug, it is essential to investigate and control the quality of Powdered Poppy Capsule Extractive (PPCE). In this paper, the qualitative and quantitative evaluation results of PPCE were obtained by using electrochemical fingerprint and high performance liquid chromatographic fingerprint. In the multi-wavelength matching average fusion chromatographic fingerprint, three parameters of macro qualitative similarity (Sc), macro quantitative similarity (Pc) and the variation coefficient of fingerprint homogeneity (α) were calculated by the limited quantified ratio fingerprint method (LQRFM). The Sc values of the samples were all greater than 0.986, the Pc values between 94.1 and 104.7, and the α values all less than 0.024 calculated by LQRFM. The calibration curve method was used to determine the contents of two markers in the samples. The loading plot of contents for two markers illustrated that the samples were divided into three categories. Firstly, the contents of morphine and codeine phosphate were below 9.3% and 4.20% in Group I (S2, S3, S6, S8, S27 and S30). Secondly, the codeine phosphate contents of Group II (S7, S9, S10, S16, S20, S24, S28 and S29) were less than 4.2%, but the morphine contents were over 9.3%.Finally, Samples with codeine phosphate content higher than 4.2% and morphine higher than 9.3% were classified as the Group III. Combined with cluster analysis of the maximum amplitude in the electrochemical fingerprint and the content determination results of PPCE, the results showed a high similarity. This study demonstrated that the electrochemical fingerprint was suitable for the identification of traditional Chinese medicine, and LQRFM was reliable and accurate for the quality control of complex traditional Chinese medicine or its related products.

Controlled Instant Pressure Drop (DIC) Pretreatment to Enhance Fractionation and Enzymatic Saccharification of Poppy Capsule Waste

Controlled Instant Pressure Drop (DIC) Pretreatment to Enhance Fractionation and Enzymatic Saccharification of Poppy Capsule Waste

Thermochemical Conversion Behavior of Turkish Lignite/Poppy Capsule Pulp Blends in N2 and CO2 Atmospheres

In this study, Thermogravimetric Analyzer coupled with Fourier Transform Infrared Spectroscopy (TGA-FTIR) was used for the determination of the thermochemical conversion reactivity of two different types of Turkish lignite coal (Tunçbilek and Orhaneli-Gümüşpınar) and poppy capsule pulp (PCP) mixtures under pyrolysis conditions at nitrogen (N2) and carbon dioxide (CO2) atmospheres. Activation energies (Ea) and pre-exponential factors (A) were determined according to Coats-Redfern method and first-order reaction model. In CO2 atmosphere, all samples exhibited an extra weight loss around 800 - 850 ° C, different from the N2 atmosphere, due to the reactive nature of CO2 during thermal decomposition. FTIR analysis confirmed this finding, at high temperatures CO formation were observed in the CO2 atmosphere. In all mixtures, the third zone experimental decomposition temperature is lower than that obtained theoretically in N2 atmosphere, showing that there might a synergistic interaction between the PCP and the lignite samples. The Ea of PCP/Tunçbilek lignite mixtures are smaller than the Ea of their parent components indicating synergy in N2 and CO2 atmospheres. However, initial and maximum decomposition temperatures for the parent components remain unchanged for these mixtures. Moreover, especially at temperatures higher than 600 °C, the Ea for biomass/lignite mixtures found lower than the theoretical values, due to the possible synergistic interactions between PCP and coal samples. According to FTIR analysis, CO, CH4, CHn and ether/amine components were detected. Gaseous pyrolysis product compositions were highly dependent on temperature, and gas species formation was consistent with the weight loss of samples.

Synthesis of Morphinans through Anodic Aryl-Aryl Coupling.

The morphinans are an important class of structurally fascinating and physiologically important natural products as exemplified by the famous opium alkaloids of the morphine family. Although this class of secondary metabolites from the juice of the opium poppy capsule was already used for medicinal purposes thousands of years ago, chemical modifications are still being applied to the core structure today in order to achieve the most specific effect on the various receptor subtypes possible with the fewest possible side effects. The unusual architecture of the morphinan core has also proven to be a highly challenging target for total synthesis. This review highlights electrosynthetic approaches towards natural and semisynthetic morphinan alkaloids. The historical progress in applying anodic aryl-aryl couplings to the construction of the morphinan framework is described in chronological order while particular benefits and challenges concerning the electrochemical transformations are grouped together, including the influence of substitution patterns, protecting groups, and reaction conditions.

An İn vitro Study on Anticancer Activity of Noscapine

Aims: Breast cancer is the most common type of cancer among women and ranks second among the causes of female death in the world. In order to find a solution to breast cancer, different studies are being conducted for the treatment and the effects of different drugs and substances on this disease are intensively investigated. Boric acid has been shown to control the proliferation of certain types of cancer cells.Noscapine is one of the ingredients in Papaver somniferum (opium). It was first isolated from Papaver somniferum (opium) in 1817. It is one of the most abundant opioids found in the opium plant (up to 10% of the total composition) after morphine. It is also known as Narcotine, Nectodon, Nospen, Anarcotine, and (archaic) Opiane and occurs in the (-)α isomer which has S, R stereochemistry (S stereochemistry at phthalide-carbon and R at isoquinoline-carbon). Noscapine is structurally and chemically different from other opium alkaloids such as morphine, codeine, thebaine, papaverine, and narceine.
 Materials and Methods: Based on this information, this study was conducted in vitro to optimize the pure form of noscapine (obtained from the poppy capsule) by applying different concentrations on MCF-7 breast cancer cell lines. HPLC technique which is one of the most widely analytical techniques has been used in this study. Determination of the LD50 value and cell proliferation by viability test was also performed to investigate the predicted effects of noscapine on MCF-7 breast cancer cell lines using VEGF (Vascular Endothelial Growth Factor) and PARP (Poly (ADP-Ribose) Polymerase) Analysis.
 Discussion: According to the results, it was observed in proliferation experiment that the vitality values decreased in direct proportion to the concentration and time at concentrations of 5 ppm, 10 ppm, 25 ppm, 50 ppm, 75 ppm, and 100 ppm. The LD50 value was determined as 50 ppm. There was no significant difference in VEGF values. It was also observed that the PARP level was lower than control group.
 Conclusion: As a result of the vitality test performed with the CCK-8 kit, it was determined that noscapine has an antiproliferative effect in various concentrations. The low PARP data in the noscapine groups suggests that the cell goes to apoptotic death.

A glimpse from the ancient world: What a gold necklace from Tillya-tepe reveals about opium in Afghanistan

Among the six excavated burials at Tillya-tepe, in northern Afghanistan, was one occupied by an elite woman wearing a substantial necklace consisting of large gold beads shaped as seed-heads. The scale and fine workmanship of this necklace suggest that it was one of her most important possessions. It can be demonstrated that these large seed-heads are representations of poppy capsules, whose significance lies in the fact that they are the source of the potent drug opium. This necklace is the most outstanding object within a group of items decorated with poppy imagery, all of which were discovered in female burials. The opium poppy has long been a culturally important plant, and the implication of this identification is investigated in several contexts. Firstly, the proliferation of poppy imagery in the female burials at Tillya-tepe is examined, and then there is a discussion of material evidence for opium among relevant peoples along the Eurasian steppes. The particular cultural importance of opium is reviewed, leading finally to a proposal for the societal role of these women.

Rheological behavior of bituminous binders replaced by poppy capsule pulp based bio-oil

The increased consumption of petroleum resources around the world has encouraged research on the development of alternative binders with similar rheological properties to bituminous binders. In this study, poppy capsule pulp-based bio-oil was added to bitumen at 1, 3, 5, 7, 9%, and bitumen tests were carried out. Stone mastic asphalt (SMA) mixtures with the Marshall design were used for the wearing layer with 3% bio-oil added to the bitumen specimens, and the results were compared to the control SMA. The results showed that the SMA produced using 3% bio-oil additive exhibited similar behavior to the conventional SMA specimens.

Quality evaluation of powdered poppy capsule extractive by systematic quantified fingerprint method combined with quantitative analysis of multi-components by single marker method

Powdered Poppy Capsule Extractive (PPCE) is largely used as a raw material of Compound Liquorice Tablets, but there are few studies of its quality evaluation or control. In this paper, a novel strategy for quality assessment of PPCE, systematic quantified fingerprint method (SQFM) combined with quantitative analysis of multi-components by a single marker (QAMS) method, was developed and validated. According to the outcome of Pm and the content of codeine and morphine, 41 batches of PPCEs were classified into two classifications by hierarchical cluster analysis, and the samples in one of the categories were obviously inferior to normal in quality. The results demonstrated that the strategy developed in this paper could provide a new method for quality evaluation of PPCE or even other traditional Chinese medicine (TCM).

Extraction and Determination of Morphine Present on the Surface of Australian Food Grade Poppy Seeds Using Acidic Potassium Permanganate Chemiluminescence Detection

In 2018, the European Food Safety Authority reiterated the need for continued monitoring and reduction of opium alkaloid contamination on culinary poppy seeds. In this study, we propose acidic potassium permanganate chemiluminescence as an alternative detection strategy for the selective determination of morphine on poppy seeds. Six different brands of poppy seed purchased in Australia were found to contain, on average, between 21 and 210 μg/g of morphine. Seeds removed from poppy capsules within the laboratory contained significantly less morphine than those which underwent traditional industrial processing. A high-throughput sensitive flow injection analysis (FIA) method was also developed which provided results in reasonable agreement with a high-performance liquid chromatography – chemiluminescence method and a limit of quantification of 7.1 × 10−4 μg/g. Complex samples encountered in food analyses typically require separation and selectivity in one or more steps of the analytical workflow (such as sample preparation, column separation and/or detection) to improve the confidence in the determination of the target analyte. To this end, the FIA method developed here offers a simple way for industry to rapidly monitor the morphine content of poppy seeds prior to entry into the consumer market.

Opium poppy capsule growth and alkaloid production is constrained by shade during early floral development

AbstractMorphinan alkaloids accumulate in the capsules of Papaver somniferum L. (opium poppy) most likely as defence against herbivory. Thus, capsule size is an important component of alkaloid yield. Shade during early cell division‐dominated growth of reproductive structures generally reduces final fruit size more than shade during later cell expansion‐dominated growth. The current study aimed to determine whether this response is found in opium poppy and the subsequent impact on alkaloid yield, composition and seed production. First the timing of key reproductive developmental events was resolved relative to macromorphological traits. Plants were then shaded during either (a) floral initiation, (b) early floral development or (c) capsule expansion before being harvested at maturation. Shade during floral initiation dramatically reduced final capsule size, alkaloid yield and seed number, and increased the concentration of precursor compounds relative to morphine, despite plants later returning to full sun. Shade during later capsule growth enhanced capsule size and alkaloid yield but had little effect on alkaloid composition or seed number. Thus, early developmental processes, including morphine biosynthesis, appear to have a relatively greater demand for carbohydrates compared with later processes. Crop management practices and environmental factors that limit carbohydrate availability during early development are thus predicted to have significant negative impacts on alkaloid production and reproductive success.

Cancer and Opium Addiction

Drug abuse remains a serious health and social threat in the world. According to the United Nations Office of Drugs and Crime (UNODC) 1n 2010, an estimated 16.5 million people use opium or its derivatives illicitly (1). Meanwhile, Iran has the first rank in the prevalence of opium consumption (2), and Opium is the most commonly abused drug in Iran (8). Opium is the air-dried extract obtained from the seed capsules of the opium poppy, which is used for recreational or medical purposes in different parts of the world (3). Approximately 8 to 14 percent of opium is made up of morphine, which is processed chemically to produce heroin and other synthetic opioids for medicinal use and also for drug abuse (4).

Biomass co-pyrolysis: Effects of blending three different biomasses on oil yield and quality.

In the present study, pyrolysis and co-pyrolysis of sugarcane bagasse, poppy capsule pulp, and rice husk were conducted in a fixed bed reactor at 550⁰C in nitrogen atmosphere. The moisture (5%-8%), ash (4%-17%), volatile matter (60%-76%), and fixed carbon analyses (11%-24%) of the utilized biomass were conducted. The decomposition behavior of biomasses due to the heat effect was investigated by thermogravimetric analysis/differential thermal analysis . In the pyrolysis of biomasses separately, the highest bio-oil yield was obtained with sugarcane bagasse (27.4%). In the co-pyrolysis of the binary blends of biomass, the highest bio-oil yield was obtained with the rice husk and sugarcane bagasse blends. While the mean bio-oil yield obtained with the separate pyrolysis of these two biomasses was 23.9%, it was observed that the bio-oil yield obtained with the co-pyrolysis of biomass blends was 28.4%. This suggested a synergistic interaction between the two biomasses during pyrolysis. It was observed that as the total ash content in the biomasses used in the pyrolysis increased, the bio-oil yield decreased, and the solid product content increased. Characterization studies of bio-oils were conducted by Fourier-transform infrared spectroscopy, gas chromatography-mass spectrometry (GC-MS), and hydrogen-1 nuclear magnetic resonance analyses. Results of these studies revealed that, all bio-oils were mainly composed of aliphatic and oxygenated compounds. The calorific values of bio-oils were determined by calorimeter bomb. Based on the GC-MS, the bio-oils with high fatty acid and its ester content also had high calorific values. The highest calorific value was 29.68 MJ kg-1, and this was obtained by pyrolysis of poppy capsule and sugarcane bagasse blend.

The specific abiotic and biotic damage of poppy (Papaver somniferum) — a review

The poppy (Papaver somniferum) is a very sensitive crop, suffering from specific types of abiotic and biotic damage. Herbicides, soil conditions, weather and their combination are frequent causes of abiotic damage. Specific type of herbicide deformation is spiral stem. Damage caused by sequence of registered herbicides is also known. Massive solidification of the soil can cause fat growth of root neck or beet deformation of roots. Seedless capsules as a specific poppy damage that is caused by the influence of stress factors (herbicides, soil conditions, high amount of plant chemicals) at elongation growth phase, followed by inappropriate weather at the blossom time. Atypical biotic damage can be caused by diseases Fusarium sp., Sclerotinia sclerotiorum, Botryotinia fuckeliana or bacterial infection. Visual symptoms of fusarial infection (orange colored plant parts or pinkish mycelium) occur only rarely. The often-detected traces of fusariotoxins in the seeds suggest, that the hidden infection of poppy by Fusarium is also possible. Sporadically, Sclerotinia sclerotiorum and Botryotinia fuckeliana can infect stems and capsules too. Lower intensity of bacterial infection (Erwinia carotovora ssp. carotovora) causes the black colored stem basis and root neck. Verticillium sp. causes similar symptoms and so these infections can confused for each other. If the pest damage is unusual, is questionable, because papaver stem midge (Timaspis papaveris) occurs commonly, but this pest is not too well known. The poppy capsule weevil (Neoglocianus maculaalba) is well known in the warmest growth areas and it is now extending to the colder areas too. Hares and roes cause specific biotic damage, when they eat only the buds in the elongation growth stage